LIBRARY OF CONGRESS. 



• 



Chap. Copyright No 

ShelL*£jct-. 



UNITED STATES OF AMERICA. 



J 



\ 



A MANUAL 



OF 



CLINICAL DIAGNOSIS 

BY MEANS OF MICROSCOPIC AND 
CHEMICAL METHODS, 

FOR 

STUDENTS, HOSPITAL PHYSICIANS, AND PRACTITIONERS. 



BY 

CHARLES E. SIMON, M.D., 

LATE ASSISTANT RESIDENT PHYSICIAN, JOHNS HOPKINS HOSPITAL, BALTIMORE. 



With 132 Illustrations on Wood and 10 Colored Plates 







JUL 241 Ml 









PHILADELPHIA AND NEW YORK : 

L E A B R O T H E R S & C O. 

18 96. 






Entered according to the Act of Congress, in the year 1896, by 

LEA BBOTHERS & CO., 

In the Office of the Librarian of Congress. All rights reserved. 



DORNAN, TEINTER. 



TO 



MY WIFE. 



WHO HAS SO FAITHFULLY AIDED IN TTS PREPARATION, 



AND TO 



Professor RUDOLPH v. JAKSCH, 



TO WHOM MEDICAL SCIENCE IS SO DEEPLY INDEBTED FOR ADVANCING 



THE SUBJECTS OF CLINICAL CHEMISTRY AND MICROSCOPY, 



THIS VOLUME IS DEDICATED 



BY THE 



AUTHOR, 



PREFACE. 



It is curious to note that, notwithstanding the great importance 
of clinical chemistry and microscopy, but little attention is paid to 
these subjects, either by hospital physicians or by those engaged in 
general practice. This lack of interest is referable primarily to the 
fact that a systematic study of these branches has hitherto been 
greatly neglected, not only iu American medical schools, but also in 
those of Europe. 

It is no rarity to hear physicians in general practice claim that 
they are too busy to conduct careful examinations of the urine, 
sputum, blood, gastric juice, etc. Would it not be reasonable to 
suppose, however, that a physician who is overwhelmed with work 
to such an extent that he cannot fiud the time to make use of aids 
in diagnosis which are quite as important as the stethoscope, the 
laryngoscope, or the ophthalmoscope, would be in a position to employ 
an assistant in his laboratory ? The younger practitioner is cer- 
tainly not placed in such a dilemma, and it is a fair assumption that 
he could successfully compete with his more experienced colleague, 
in matters of diagnosis at least, were he to familiarize himself suffi- 
ciently with laboratory methods of diagnosis. 

The time is at hand when the practice of medicine is becoming 
what it was long ago, but then unjustly called, a true science and art. 
jSTo continuing success can be built on empiricism or upon the propor- 
tion of guesswork which is inseparable from dependence upon " the 
experienced eye." " Diagnosis " is now the password in medical 
science. A knowledge of electro-diagnosis, of ophthalmoscopy, of 
laryngoscopy, etc., is at the present day a sine qua non for accurate 
diagnosis. Equally important at all times, and frequently even 
more important, is a knowledge of clinical chemistry and microscopy. 
It is inconceivable that a physician can rationally diagnose and 
treat diseases of the stomach, intestines, kidneys, and liver, etc., 
without laboratory facilities. 

It has been the author's aim to present to students and physicians 
those facts in clinical chemistry and microscopy which are of practical 



v iii PREFACE. 

importance. With the hope of exciting interest in these unjustly 
neglected subjects, he has not confined himself to bare statements of 
fact, which must in themselves be dry and uninteresting, but he has 
attempted to point out the reasons which have led up to the conclu- 
sions reached. 

Chemical and microscopic methods are described in detail, so that 
the student and practitioner who have not had special training in such 
manipulations will be enabled to obtain satisfactory results. 

The subject-matter covers the examination of the blood, the 
secretions of the mouth, the gastric juice, feces, nasal secretion, spu- 
tum, urine, transudates, exudates, cystic contents, semen, vaginal 
discharges, and milk. In every case a description of normal mate- 
rial precedes the pathologic considerations, which latter in turn are 
followed by an account of the methods used in examination. A 
glance at the table of contents will furnish an idea of the various 
subjects considered under each heading. 

It was not deemed advisable to burden the volume with a com- 
plete enumeration of the various literary sources consulted by the 
author in its preparation, and the names of the various investigators 
mentioned in the text have been largely introduced as a matter of 
historical interest. 

In conclusion it is the agreeable duty of the author to express his 
sincerest thanks to his wife for assistance without which this volume 
could not have been written, and likewise for those illustrations 
which are original; to Dr. William H. Welch for his kindness in 
placing the former Hygienic Laboratory of the Johns Hopkins 
Hospital at his disposal during the years 1892 and 1893 ; to Dr. 
W. Milton Lewis for much valuable aid in the correction of the 
manuscript and proof-sheets; and to Messrs. Lea Brothers & Co. 
for the typographical excellence of the work, the extremely satis- 
factory reproduction of the drawings, and for many acts of courtesy. 

CHARLES E. SIMON. 

Baltimore, Md., 1896. 



CONTENTS. 



CHAPTER I. 



THE BLOOD. 

PAGE 

General considerations ..... ..... 17 

General characteristics of the blood 17 

color 17 

odor 18 

specific gravity 18 

reaction ............ 20 

Chemical examination of the blood 23 

general chemistry of the blood 23 

blood-pigments .26 

hemoglobin .......... 26 

oxyhemoglobin ......... 27 

estimation of hemoglobin with FleischFs hemometer . 29 

estimation of hemoglobin with Gowers's hemoglobinometer 32 

hemoglobinemia ....... 33 

carbon monoxide hemoglobin ..... 34 

nitric oxide hemoglobin ........ 34 

sulphuretted hydrogen hemoglobin 35 

carbon dioxide hemoglobin 35 

hematin 35 

hemin 36 

methemoglobin .......... 37 

hematoidin 38 

hematoporphyrin .38 

the spectroscope .... .... 38 

the proteids of the blood 40 

the carbohydrates .......... 41 

sugar 41 

glycogen 42 

cellulose ........... 43 

urea 43 

uremia 43 

uric acid and the xanthin bases ....... 44 

fat and fatty acids .......... 45 

lactic acid 46 

biliary constituents . 47 

acetone . . . . *" . . . . . . . .48 

Microscopic examination of the blood 48 

the red corpuscles 48 

variations in the size of the red corpuscles .... 48 

variations in the form of the red corpuscles .... 49 
variations in the number of the red corpuscles . . .4!) 

nucleated red corpuscles 50 



CONTENTS. 



Microscopic examination of the blood — 

the leucocytes 

variations in the number of the leucocytes 

physiologic hyperleucocytosis 

pathologic hyperleucocytosis 

general differentiation of the various forms of leucocytes 

the anilin-stains 

differentiation of the leucocytes according to their behavior 

toward anilin-stains 

the drying and staining of blood 

staining with eosin 

staining with Ehrlich's tri-glycerine mixture 
staining with Ehrlich's hsematoxylin-eosin 
staining with Ehrlich's tri-acid stain 
staining with Aronsohn and Philips's modified tri-acid 
stain ......... 

staining with Chenzinsky-Plehn's mixture 
staining with Ehrlich's neutral mixture 
special staining of basophilic leucocytes . 

the plaques 

the enumeration of the corpuscles of the blood by the method 

Thoma-Zeiss .... 

enumeration of the red corpuscles . 
enumeration of the white corpuscles 
indirect enumeration of the leucocytes 
the hsematokrit .... 

Bacteriology and parasitology of the blood 
acute miliary tuberculosis 
glanders 



typhoid fever 
influenza . 



sepsis 

relapsing fever . 

anthrax 

malaria 

nielansemia 

filaria sanguinis hominis 

distoma haematobium 



of 



51 
52 
53 
55 

56 
57 

57 
60 
62 
62 
62 
62 

63 

63 
64 
64 

64 

65 
65 
67 
69 
69 
72 
73 
73 
74 
74 
75 
75 
76 
77 
82 
83 
84 



CHAPTER II. 



THE SECRETIONS OF THE MOUTH. 

Saliva g$ 

general characteristics ' . .86 

chemistry of the saliva 8Q 

microscopic examination of the saliva ! 88 

pathologic alterations 89 

the saliva in special diseases of the mouth . . . . ! 90 

catarrhal stomatitis .90 

ulcerative stomatitis .90 

thrush ' \ ' 90 

Tartar ' 91 

Coating of the tongue [ 91 

Coating of the tonsils \ " 91 

pharyngomycosis leptothricia ........ 91 

diphtheria 91 



CONTENTS. 



\i 



ciiAP'rai in. 



THE GASTRIC JUICE AND THE GASTRIC CONTENTS. 

The secretion of gastric juice . 
Test-meals 

the test-breakfast of Ewald and Boas 

the test-dinner of Riegel . 

the double test-meal of Salzer . 
the test-breakfast of Boas 

The stomach-tube 

Contraindications to the use of the tube 

The introduction of the tube . 

General characteristics of the gastric juice 

Amount 

Chemical examination of the gastric juice 
chemical composition of the gastric juice 
the acidity of the gastric juice 
determination of the acidity of the gastric juice 
the source of the hydrochloric acid 
significance of the free hydrochloric acid 
the amount of free HC1 . 

euchlorhydry 

hypochlorhydry 

anachlorhydry . 

hyperchlorhydry 
test for free acids 
tests for free hydrochloric acid 

the diinethyl-amido-azo-benzol test 

the phloroglucin-vanillin test . 

the resorcin test 

the methyl-violet and emerald-green test 

the tropseolin test 

Mohr's test 

the benzopurpurin test 
the combined hydrochloric acid 
the quantitative estimation of the hydrochloric acid of gastric 

Topfer's method 

Martius and Liittke's method 

Leo's method 
the ferments of the gastric juice and their zymogens 

pepsin and pepsinogen 

tests for pepsin and pepsinogen 

quantitative estimation 

chymosin and chymosinogen 

tests for chymosin and chymosinogen 

quantitative estimation 
the products of gastric digestion 

the digestion of native albumins 

the digestion of the albuminoids 

the digestion of carbohydrates . 

the digestion of fats . 
analysis of the products of albuminous digestion 
analysis of the products of carbohydrate digestion 
lactic acid . . . . ' . 

mode of formation and clinical significance 
tests for lactic acid .... 
Uffelmann's test .... 

Kelling's method .... 



juice 



PAGE 

94 
95 
96 
96 
96 
97 
97 
97 
98 
100 
100 
101 
101 
102 
104 
107 
108 
110 
110 
110 
110 
111 
111 
112 
112 
113 
114 
114 
114 
114 
115 
115 
117 
117 
119 
122 
123 
123 
125 
125 
126 
128 
128 
128 
128 
130 
130 
131 
132 
134 
134 
134 
137 
137 
138 



Xll 



CONTENTS. 



Chemical examination of the gastric juice — 

Strauss's method 138 

Boas's method 139 

quantitative estimation of lactic acid according to Boas's 
method . . . . . . ... . . .140 

the fatty acids 142 

mode of formation and clinical significance .... 142 

tests for butyric acid 144 

tests for acetic acid . . . . _ 144 

quantitative estimation of the fatty acids 144 

quantitative estimation of the organic acids .... 144 

gases 145 

acetone 147 

ptomaines and toxalbumins 148 

vomited material . 148 

food-material 148 

mucus 149 

saliva 150 

bile . 150 

pancreatic juice 150 

blood 150 

pus 151 

stercoraceous material 151 

parasites 152 

the odor . . 152 

Microscopic examination of the gastric contents 152 

Examination of the motor power of the stomach 155 

Leube's method 155 

the salol test of Ewald and Sievers 155 

Examination of the resorptive power of the stomach .... 156 

Indirect examination of the gastric juice 157 

Giinzburg's method 157 

the author's method 157 





CEL 


1PTEK IV. 






THE FECES. 


Definition 160 


Examination of the normal feces 






160 


general characteristics 






160 


number of stools 








160 


amount 








160 


consistence 








161 


odor . 








161 


color . 








161 


macroscopic constituents 








161 


alimentary detritus 








161 


foreign bodies . 








162 


microscopic constituents 








162 


constituents derived from food . 




162 


morphologic elements derived from the alimentary canal 




163 
163 


parasites 








164 


vegetable parasites 








164 


fungi . 








165 


schizomycetes 








165 


bacteria 








165 



CONTENTS. 



XIII 



Examination of the normal feces — 














chemistry of normal feces ........ 1<><> 


reaction 












L66 


general composition . 












Kit; 


phenol, iiulol, ami skatol . 












168 


Fatty acids 












170 


cholesteiin .... 












171 


the biliary acids 












173 


pigments ..... 












173 


Pathol oir v of the feces .... 












174 


general characteristics .... 












174 


number of stools 












174 


consistence 












175 


amount 












175 


odor 












175 


reaction 












175 


color 












175 


macroscopic constituents . 












177 


alimentary constituents 












177 


mucus and mucous cylinders 












177 


biliary and intestinal concretions 












178 


analysis of gall-stones 












179 


microscopic examination . 












180 


technique 












180 


remnants of food 












180 


epithelium .... 












181 


red blood-corpuscles . 












181 


leucocytes 












. 181 


crystals 












181 


animal parasites .... 












182 


protozoa ..... 












183 


vermes 












187 


insecta ..... 












. 197 


vegetable parasites .... 












. 197 


chemistry of the feces 












. 201 


The physiology of diarrhoea and constipation 












. 202 


diarrhoea 












. 202 


constipation 












204 


The feces in various diseases of the intestinal 


tract 










. 205 


acute intestinal catarrh 












. 205 


chronic intestinal catarrh 












206 


cholera nostras 












. 207 


intestinal catarrh of infants 












. 207 


dysentery 












207 


amoebic dysentery .... 












. 207 


cholera asiatica .... 












. 208 


typhoid fever 












. 209 


Meconium 












. 209 



CHAPTER V. 

THE NASAL SECRETION. 



Definition .... 

The physiology and pathology of 



210 

210 



xiv CONTENTS. 



CHAPTER VI. 

SPUTUM. 



PAGE 

Definition 211 

General technique 211 

General characteristics of the sputa 212 

amount 212 

consistence 213 

color 213 

odor • 214 

specific gravity 215 

configuration of sputum 215 

Macroscopic constituents of sputum 216 

elastic tissue 216 

fibrinous casts 217 

Curschmann's spirals 218 

echinococcus membranes . 220 

concretions 220 

foreign bodies • 220 

Microscopic examination 220 

leucocytes 220 

red blood-corpuscles 221 

epithelial cells 221 

elastic tissue 223 

animal parasites 224 

vegetable parasites 225 

pathogenic organisms 225 

the tubercle bacillus 225 

methods of staining . 227 

Weigert-Ehrlich's method . . . . . .228 

Gabett's method 228 

Ziehl-Neelsen's method 228 

the diplococcus pneumoniae 229 

the bacillus of influenza 230 

the bacillus of whooping-cough . . . . . . 230 

actinomycosis 230 

non-pathogenic organisms 231 

crystals - 231 

Charcot-Leyden's crystals . . . . • . . . 231 

hsematoidin 232 

cholesterin 232 

fatty-acid crystals 232 

leucin and tyrosin crystals 232 

calcium oxalate 232 

triple phosphates 233 

Chemistry of the sputum . . . 233 

The sputa in various diseases 234 

acute bronchitis 234 

chronic bronchitis 234 

putrid bronchitis and pulmonary gangrene 234 

fibrinous bronchitis . . . . . . . . . 235 

bronchial asthma . . . . . . . . . 235 

pulmonary abscess 235 

abscess of the liver with perforation into the lung .... 235 

pneumonia . . . . * 236 

phthisis pulmonalis ......... 236 

oedema of the lungs 237 

heart-disease 237 



CONTENTS. 



w 



The sputa in various diseases — 
the pneumoconioses 
anthracosis 
Biderosis . 
chalicosis 
stycosis 



CIIAITKK VII. 



urine 



THE I'lMNi:. 
General considerations 
General characteristics of tlu 

general appearance 

color 

odor 

consistence 

quantity . 

polyuria . 

oliguria 
specific gravity 

determination of the specific gravity . . 

determination of the solid constituents . . 

reaction ............ 

determination of the acidity of the urine .... 

The chemistry of the urine ......... 

general chemical composition of the urine ..... 

quantitative estimation of the mineral ash of the urine 

the chlorides ........... 

tost for the chlorides in the urine 

quantitative estimation of the chlorides by the method of Sal- 
kowski-Volhard ......... 

direct method 

estimation of the chlorides after incineration according to 

Neubauer and Salkowski 

the phosphates .......... 

test for the phosphates in the urine ..... 

quantitative estimation of the total amount of phosphates 

separate estimation of the earthy and alkaline phosphates 

removal of the phosphates from the urine 
the sulphates ........ 

tests for the sulphates in the urine . 

quantitative estimation of the sulphates . 

quantitative estimation of the total sulphates 
quantitative estimation of the conjugate sulphates 
urea ...... 

properties of urea . 

separation of urea from the urine 

quantitative estimation of urea 

estimation of nitrogen 
uric acid ..... 

properties of uric acid 

tests for uric acid 

quantitative estimation of uric acid 
hippuric acid 

properties of hippuric acid 

quantitative estimation of hippuric acid 
kreatin and kreatinin 

properties of kreatin and kreatinin 

test for kreatinin in the urine . 

quantitative estimation of kreatinin in the urine 



PAGE 

238 
238 
238 
238 
238 



239 

240 

240 
241 
242 
243 
243 
244 
246 
247 
250 
252 
253 
257 
258 
258 
259 
260 
263 

263 

268 

269 
270 
275 
277 
280 
280 
280 
284 
285 
285 
286 
287 
296 
298 
300 
309 
311 
315 
317 
317 
322 
324 
325 
326 
327 
328 
329 



XVI 



CONTENTS. 



The chemistry of the urine — 
the xanthin bases . 
oxalic acid 

properties of oxalic acid 
test for oxalic acid . 
quantitative estimation of oxalic acid 
the albumins .... 
serum-albumin 
serum-globulin 
albumoses (peptones) 
haemoglobin 

fibrin .... 

nucleo-albumin 
histon .... 
tests for the albumins 

tests for serum-albumin 
nitric-acid test . 
boiling-test 

potassium ferrocyanide test 
trichloracetic-acid test 
picric-acid test . 
Spiegler's test 

special test for serum-albumin 
quantitative estimation of albumin 
old method of boiling 
Esbach's method 
differential density method 
gravimetric method . 
test for serum-globulin and its quantitative estimation 
tests for albumoses 
tests for peptones 
tests for (mucin) nucleo-albumin 
tests for haemoglobin 
Heller's test 
the guaiacum test 
test for fibrin 
carbohydrates 
glucose 

tests for sugar . 
Trommer's test 
Fehiing's test 

Bottger's test with Xylander's modification 
fermentation-test 
phenyl-hydrazin test 
polarimetric test 
quantitative estimation of sugar 
Fehiing's method 
differential density method 
Einhorn's method 
polarimetric method 
lactose 
levulose . 



maltose . 
dextrin 
laiose 

animal gum 
inosit 
urinary pigments and chromogem 



CONTENTS. 



xvn 



The chemistry of the urine — 










normal pigments 384 


urochrome 








884 


uroerythrin 








385 


normal chromogens . 








886 


indicao 








386 


nrohsematui 








890 


uroroseinogen . 








391 


pathologic pigments and chromogens 






392 


blood-pigments . 








392 


hfematin 








392 


urorubrohrematiu and urofuscohiematin 






392 


uroha?matoporphyrin . . » 






393 


biliary pigments ..... 






393 


Smith's test 






395 


Huppert's test 






395 


( imelin's test, as modified by Rosenbach 






396 


Gnielin's test ..... 






396 


biliary acids 






396 


cholesterin 






396 


pathologic urobilin ..... 






396 


melanin and melanogen .... 






398 


phenol urines ...... 






399 


alkapton 






399 


blue urines ...... 






400 


green urines ...... 






400 


pigments referable to drugs 






400 


Ehrlich's reaction 






. 401 


conjugate sulphates ...... 






405 


skatoxyl 






405 


phenol and paracresol 






405 


pyrocatechin 






407 


acetone 






407 


tests for acetone ...... 






408 


Legal's test 






408 


Lieben's test 






408 


Reynold's test 






408 


diacetic acid 






408 


oxybutyric acid 






. 409 


lactic acid ........ 






410 


volatile fatty acids 






410 


chyluria ......... 






410 


ferments ......... 






411 


gases 






. 411 


ptomaines 






. 412 


sediments ........ 






. 412 


Microscopic examination of the urine .... 






416 


non-organized sediments ...... 

sediments occurring in acid urines . 






. 416 






416 


uric acid 






416 


amorphous urates 






418 


calcium oxalate 






418 


ammonio-magnesium phosphate 






120 


monocalcium phosphate .... 






421 


neutral calcium phosphate 






421 


basic magnesium phosphate 






421 


hippuric acid 






122 


calcium sulphate 








123 



XV111 



CONTENTS. 



Microscopic examination of the urine — 

cystin .... 

leucin and tyrosin 

xanthin .... 

soajDs of lime and magnesia 

bilirubin and haematoidin 

fat 

sediments occurring in alkaline urine 

basic phosphates of calcium and magnesium 

ammonium urate . 

magnesium phosphate 

ammonio-magnesium phosphate 

calcium carbonate 

indigo 
organized constituents of urinary sediments 
epithelial cells 
leucocytes 

red blood-corpuscles 
tube-casts 

true casts . 

hyaline casts 

waxy casts 

pseudo-casts 

cylindroids 

formation of tube-casts 

clinical significance of tube-casts 
spermatozoa 
parasites . 

vegetable parasites 

animal parasites 
tumor particles 
foreign bodies . 



CHAPTEK VIII. 



TRANSUDATES AND EXUDATES. 

Definition .... 
Transudates .... 
general characteristics 
specific gravity 
chemistry of transudates 
microscopic examination 
Exudates .... 
serous exudates 
hemorrhagic exudates 
tuberculosis 
cancer 
putrid exudates 

pus 

general characteristics of pus 
the chemistry of pus 
microscopic examination of pus 
leucocytes . 
giaut corpuscles 
detritus 

red blood-corpuscles 
pathogenic vegetable parasites 



CONTENTS. 



xix 



Exudates — 



protozoa 
vermes 

crystals 



PAG] 

469 
469 
470 



CHAPTER IX. 

THE EXAMINATION OF CYSTIC CONTENTS. 



Cysts of the ovaries and their appendages 
Hydatid cysts . . • ' . 

Hydronephrosis ..... 
Pancreatic evsts 



471 
472 
473 
473 



CHAPTER X. 

THE EXAMINATION OF MENINGEAL FLUID. 



Definition 
In disease 



474 
474 



CHAPTER XI. 

THE SEMEN. 



Definition ...... 

General characteristics .... 

The chemistry of the semen . 

The microscopic examination of the semen 

The pathology of the semen . 

The recognition of semen in stains 



475 
475 
475 
476 
477 
477 



CHAPTER XII. 



THE VAGINAL DISCHARGES. 



General description 

Vaginal blennorrhcea 

Menstruation 

The lochia 

Vulvitis and vaginitis . 

Membranous dysmenorrhea 

Cancer .... 

Gonorrhoea 

Abortion 



479 

480 
480 
480 
481 
481 
482 
482 
482 



CHAPTER XIII. 

THE SECRETION OF THE MAMMARY GI 

The secretion of milk in the newly born 
Colostrum ....... 

The secretion of milk proper in the adult female 

Human milk 

The milk in disease 

The examination of cow's milk 

determination of the specific gravity 

the estimation of fat ... 



A.NDS. 



484 
484 
485 
485 
486 
487 
487 
489 



CLINICAL DIAGNOSIS. 



CHAP TEE I. 

THE BLOOD. 

GENERAL CONSIDERATIONS. 

If blood be allowed to flow directly from au artery into a vessel 
surrounded by a freezing-mixture, and containing one-seventh of its 
own volume of a saturated solution of sodium sulphate, or a 25 per 
cent, solution of magnesium sulphate (one volume to four volumes 
of blood), it will be observed that after some time a sediment, pre- 
senting the ordinary color of arterial blood, has formed at the bottom, 
covered by a layer of clear, straw-colored fluid, the blood-plasma. 

Upon microscopic examination the sediment will be seen to con- 
tain : 

o. Numerous homogeneous, non-nucleated, circular, biconcave 
disks. These measure on an average 7.5 t± in diameter, and are of 
a faint greenish-yellow color when viewed through the microscope, 
while en masse they present the color of arterial blood : the erythro- 
cytes or red corpuscles of the blood. 

6. Roundish or irregularly shaped nucleated cells. These are far 
less numerous than the red corpuscles, aud devoid of coloring-matter : 
the leucocytes, colorless or white corpuscles of the blood. 

c. Minute colorless disks, measuring less than one-half of the 
diameter of a red corpuscle : the so-called plaques, or blood-plates 
of Bizzozero. 

GENERAL CHARACTERISTICS OF THE BLOOD. 

The Color. 

Chemical examination of the blood has shown that its color is 
referable to the presence of an albuminous, iron-containing substance, 
hemoglobin, contained in the bodies of the red corpuscles, which is 



IS CLINICAL DIAGNOSIS. 

characterized by its great avidity for oxygen, forming a compound 

therewith, known as oxyhemoglobin. The relatively larger amount 
of the latter encountered in the arteries, as compared with the veins. 
causes the difference in the appearance of arterial and venous blood, 
the former presenting a bright scarlet-red, the latter a dark-bluish 
color. A bright cherry-red color of the blood is noted in cases of 
poisoniug with carbon monoxide, while a brownish-red or chocolate 
color is observed in cases of poisoning with potassium chlorate, ani- 
line, hydrocyanic acid, and nitrobenzol. A somewhat milky appear- 
ance is frequently seen in cases of well-marked leukaemia, and the 
author recalls an instance in which attention was first directed to the 
existence of this disease by the peculiarly milky appearance of a drop 
of blood obtained for the purpose of a haemoglobin estimation. In 
chlorosis and hydremic conditions, as would be expected, the blood 
looks pale and watery. 

The Odor. 

Tne peculiar odor of the blood, which differs greatly in different 
animals, the halitus sanguinis of the ancients, is dependent upon the 
presence of certain volatile fatty acids, and may be rendered more 
distinct by the addition of concentrated sulphuric acid. 

The Specific Gravity. 

The specific gravity of the blood in healthy adults varies between 
1.046 and 1.067, being higher on an average in men, 1.055. than in 
women, 1.054, and children — boys 1.052, girls 1.050. It is dimin- 
ished to a certain extent by fasting, the ingestion of solids and liquids, 
gentle exercise, pregnancy, etc. The specific gravity, moreover, de- 
pends upon the bloodvessel, from which the specimen is taken, being 
higher, generally speaking, in venous than in arterial blood. 

Lnder pathologic conditions the specific gravity may vary between 
1.025 and 1.068. In nephritis, chlorosis, and the anaemias in gen- 
eral, it may diminish to 1.031, as also in cachectic conditions (pul- 
monary phthisis, carcinoma of the stomach, etc. i. An increased 
specific gravity is met with, on the other hand, in febrile diseases, 
typhoid fever 1.057 to 1.063, conditions associated with pronounced 
cyan sis iphysema, fatty heart, uncompensated valvular disease, 
1.054 to 1.068), and obstructive jaundice, 1.062. 



THE BLOOD. 1<j 

Method of Determining the Specific Gravity of the Blood* 

Roy's Method. A number of test-tubes are filled with a mix- 
tare of glycerine and water in different proportions, so that the spe- 
cific gravity in the different tubes shall vary between L.025 and 1.068. 
Blood is then drawn from the tip of the finger, or the lobe of the 
ear, into a capillary tube connected with an ordinary hypodermic 
syringe, pressure being carefully avoided. A drop of blood is placed 
in each tube, in which it will sink as loug as the specific gravity of 
the glycerine mixture is lower than that of the blood, while it will 
remain suspended in a mixture the specific gravity of which is equiv- 
alent to its own. 

Eoy states that it is important for the purpose of comparison to 
make such examinations in every case at the same hour, as the spe- 
cific gravity of the blood has been shown to undergo diurnal varia- 
tions. 

The Method of Hammerschlag. A cylinder, measuring 
about 10 cm. in height, is partly filled with a mixture of chloroform 
(sp. gr. 1.526) and benzol (sp. gr. 0.889), presenting a specific 
gravity of 1.050 to 1.060. Into this solution a drop of blood is 
allowed to fall directly from the finger, pressure being avoided, and 
care being taken that the same does not come in contact with the 
walls of the vessel. The drop, moreover, should not be too large, 
as it will otherwise separate into several droplets, giving rise to inac- 
curate results. Should the drop sink to the bottom, it is apparent 
that the specific gravity of the mixture is lower than that of the 
blood, necessitating the addition of more chloroform, which should 
be added drop by drop, the vessel meanwhile being continually agi- 
tated, so as to insure a thorough diffusion of the reagents. If, on 
the other hand, the drop of blood should tend toward the surface, it 
is best to add an amount of benzol sufficient to cause the blood to 
sink to the bottom, and then to bring it to the proper degree of sus- 
pension by the subsequent addition of chloroform. As soon as the 
drop remains suspended in the mixture this is filtered and its 
specific gravity ascertained by means of an ordinary areometer. This 
will express the specific gravity of the specimen of blood examined. 

The chloroform-benzol mixture may be kept indefinitely. 

With a little practice, results sufficiently accurate for clinical pur- 
poses may thus be obtained with an expenditure of but very little 
time. 



20 



CLIXICAL DIAGXOSIS. 



Schmaltz and Peeper's Method. Where delicate scales are 
available the method of Schmaltz and Peiper may be employed, being 
the most accurate : A capillary tube, measuring about 12 cm. in 
leugth, 1.5 mm. in width, with its ends tapering to a diameter of 
0. 75 mm., is filled with blood and carefully weighed, when the weight 
of the blood, divided by the weight of an equivalent volume of dis- 
tilled water, will indicate the specific gravity. 

As Siegl and Schmaltz have shown that the specific gravity of 
the blood varies with the amount of haemoglobin, it is apparent that 
a determination of the amount of the latter may, in a manner, be 
replaced by a determination of the specific gravity. 

Direct Estimation of the Solids of the Blood. Five 
drops of blood (0.2 to 0.3 gramme), obtained by means of a fairly 
deep incision, or puncture, into the tip of the finger, moderate pres- 
sure being made upon the middle phalanx, if necessary, are collected 
in a watch-crystal. This is at once covered with its fellow, the two 
being held together by means of a spring, and weighed. The speci- 
men (open) is then dried at a temperature of from 60° to 70° C. for 
twenty-four hours, and again weighed, the weight of the solids 
being thus ascertained. 

In healthy adults the following values were obtained by Stintzing 
and Gumprecht : 

Average. Maximum. Minimum. Average water. 
In men . . 21.6 23.1 19.6 78.4 per cent. 

In women . . 19.8 21.5 18.4 80 2 " 

In conditions associated with chronic anaemia, the solids, as would 
be expected, are always considerably diminished. In leukaemia, on 
the other hand, owing to the large number of leucocytes present, a 
relative increase is observed. 

The Reaction. 

The reaction of the blood during life, owing to the presence of 
disodium phosphate, Xa 2 HP0 4 , and sodium bicarbonate, XaHCG 3 , 
is alkaline, the degree of alkalinity in terms of XaOH under normal 
conditions corresponding to 182 to 218 mgrms. for every 100 cc. of 
blood. Von Jaksch gives 260 to 300 mgrms. as the normal, and 
Canard 203 to 276 mgrms. 

The alkaline reaction of the blood may be demonstrated by repeat- 
edly drawing a strip of red litmus-paper, thoroughly moistened with 
a concentrated solution of common salt, through the blood, and rap- 



THE B LOO Ik 2] 

idly washing off the corpuscles with the same solution, when, as a 
genera] rule, the alkaline reaction can be clearly made out. 

Small plates of plaster-of -Paris or clay, stained with neutral litmus- 
solution may be similarly employed, the blood in this ease being 
washed off with water. 

Generally speaking, the alkalinity of the blood is lower in women 
and children than in men, and is, furthermore, influenced by the 
process of digestion, exercise, etc. At the beginning of digestion, 
when hydrochloric acid is being secreted in large amounts, the 
alkalinity of the blood increases; while later on, when both hydro- 
chloric acid and peptones are reabsorbed, the alkalinity in turn 
diminishes. 

A decrease is observed following violent muscular exercise, such 
as forced marches in the case of soldiers, owing in all probability to 
an excessive production of acids in the muscles. 

Under pathologic conditions a diminished alkalinity of the blood 
is frequently observed, which is particularly marked in cases of pro- 
nounced anaemia, 108 to 145 mgrms. of JSTaOH, increasing as the 
number of red corpuscles and the amount of haemoglobin diminish. 
In cases of chlorosis, however, the diminution in the number of 
red corpuscles is accompanied by a normal, or but slightly dimin- 
ished, alkalinity of the blood as a whole. In leukaemia, pernicious 
anaemia, nephritis when accompanied by uraemia, various hepatic 
diseases, diabetes, carcinoma, the various profound cachexiae, pseudo- 
leukaemia, poisoning with carbon monoxide, and acids, and finally 
in high fever, as in typhoid fever, and toxic processes in general, 
the alkalinity of the blood is diminished, the lowest value found cor- 
responding to 108 mgrms. of XaOH. A similar decrease follows 
the prolonged use of acids, while an increase is brought about by 
the ingestion of alkalies. 

There can be no doubt that results of decided clinical value 
would accrue from a systematic study of the degree of alkalinity of 
the blood in the clinical laboratory. Unfortunately, however, our 
present methods of investigation are still too complicated for daily 
use, and only applicable for purely scientific purposes. 

Von Jaksch employs the following method, a modification of that 
originally devised by Laudois : Eighteen watch-crystals are prepared, 
each containing a mixture of a concentrated solution of sodium sul- 
phate and a jfa and a y-goir normal solution of tartaric acid in 
varying proportions, so that crystal 



II. 


tt 


tt 


0.8 


III. 


•' 


it 


0.7 


IV. 


ft 


" 


0.6 


V. 


tt 


tt 


0.5 


VI. 


" 


t> 


0.4 


VII. 


tt 


it 


0.3 


VIII. 


It 


" 


02 


IX. 


11 


tt 


0.1 


X. 


tt 


tt 


09 


XI. 


« 


>t 


O.S 



22 CLINICAL DIAGNOSIS. 

No. Cc. Cc 

I. Shall contain 0.9 of the y^y norm. sol. of the acid, and 0.1 of the cone. Xa 2 S0 4 sol. 

t. I, tt tt It Q2 " " " 

it tt tt it a o g tt n tt 

tt tt tt tt tt Q.4 tt a tt 

tt tt f tt tt Q^ tt .t .t 

.« tt tt u u o.6 " " " 

a tt t: it it Q •• 'i tt ii 

tt tt .t .t tt Q_g tt tt tt 

tt tt tt tt a Q9 tt tt tt 

1 t; a i« it n i it a it 

it i' it tt o.2 " " " 

etc., for every cc. of the mixture. 

Blood is taken, preferably from the back, by means of cupping-* 
glasses, and, before it coagulates, 0.1 cc. is added to every cc. of the 
mixture described, when the reaction is determined in every crystal 
by means of very sensitive litmus-paper. The amount of acid con- 
tained in the specimen exhibiting a neutral reaction in terms of XaOH 
will then indicate the degree of alkalinity of the blood. 

As 150 (molecular weight) parts by weight of tartaric acid (C 4 H 6 6 ) 
combine with (SO (molecular weight) parts by weight of XaOH, or 75 
with 40, according to the equation : 

,COOH COOXa 

C.,H.,(OH) 2 ( +2XaOH = C,Ho(OH).< +2H 9 

x COOH x COONa 

a normal solution would contain 75 grammes of pure tartaric acid 
to the liter and a ^wo an( ^ a iwo norm al solution, respectively, 
0.75 and 0.075 gramme. As 1000 cc. of a T ^ normal solution 
would correspond to 0.4 gramme of XaOH, and 1000 cc. of a 10 1 00 
normal solution to 0.04 gramme, 1 cc. of the y^ normal solution 
will represent 0.0004, and 1 cc. of the y^- normal solution 0.00004 
gramme of XaOH. 

Supposing then a neutral reaction to have been obtained in the 
crystal containing 0.6 cc. of the T ^ normal solution, the alkalinity 
of the 0.1 cc. of blood in terms of XaOH would correspond to 
0.00024 gramme of XaOH, or 0.24 gramme to 100 cc. of blood. 

As the alkalinity of the blood rapidly diminishes after being 
drawn, owing, in all probability, to the formation of an acid caused 
by the decomposition of the haemoglobin, it is apparent that the 
experiment must be performed as rapidly as possible, not more than 
one minute and a half being allowed to elapse between the taking of 
the blood and the conclusion of the experiment. 



Man. 


Woman. 


513.01 


369.2 


349.7 


272.6 


159.6 


120.1 


3.7 


3.55 


486.9 


603.8 


439.0 


552.0 


3.9 


1.91 


39.9 


44.79 


4.14 


5.07 



THE BLOOD. 23 

This method is, oi course, not free from objections, but sufficiently 
accurate for clinical purposes. 

CHEMICAL EXAMINATION OF THE BLOOD. 

General Chemistry of the Blood. 

A general idea of the chemical composition oi' the blood may he 
Formed from the accompanying table of C. Schmidt, calculated for 
1000 parts : 

Corpuscles 

Water 

Haemoglobin and globulins 

Mineral salts .... 
Plasma 

Water 

Fibrin ... . 

Albumins and extractives . 

Mineral salts .... 

If blood be allowed to flow iuto a vessel aud set aside, it will be 
observed that at the expiration of a few minutes the entire mass has 
become transformed into a semi-solid, gelatinous material, which is 
spoken of as the blood-clot, or the placenta sanguinis. Still later it 
will be seen that a small amount of straw-colored fluid has appeared 
on top of the clot, which gradually increases in amount, while the 
clot itself uudergoes shrinkage, until finally the latter, greatly dimin- 
ished in size, floats in the surrounding fluid. The straw-colored 
fluid which has thus been obtained during the process of coagulation 
is spoken of as the blood-serum. 

If, furthermore, a bit of the clot be examined microscopically, this 
will be seen to consist of a more or less dense network of fibres, the 
meshes of which are filled with blood-corpuscles, which may be 
washed out, leaving the fibrous network, fibrin, behind. 

Chemically speaking, fibrin belongs to the class of so-called coag- 
ulated albumins, and probably does not occur in the circulating blood, 
being formed only during the process of coagulation. 

The albumins which are found in plasma are fibrinogen, serum- 
globulin, and serum-albumin, and while serum-globulin and serum- 
albumin are likewise encountered iu the serum, the fibrinogen has 
disappeared, and traces of a new albuminous body, fibrino-globulin, 

1 This figure is too high ; in man it varies between 420 and 470 for 1000 parts of blood. 



24 



CLINICAL DIAGNOSIS. 



are found. There appears to be no doubt that the fibrin has resulted 
from the fibrinogen by a process of disassociation, traces of a soluble 
albumin, fibrino-globulin, being formed at the same time. Modern 
researches, furthermore, have shown that the transformation of fibrino- 
gen into fibrin is dependent upon the action of a ferment, the fibrin- 
ferment, derived in all probability from the leucocytes of the blood 
by a process of plasmoschisis. The presence of serum-globulin ap- 
parently hastens coagulation in an indirect manner, as is done by 
calcium chloride and the calcium salts in general. 

Under normal conditions blood clots in from two to six minutes 
after being shed, while in disease, notably in hemophilia, coagula- 
tion may be greatly delayed, or even not occur at all, so that fatal 
hemorrhage may follow the infliction of trifling wounds. Whether 
or not this condition is referable to certain abnormalities in the chem- 
ical composition of the blood is as yet undetermined. 

A tendency to hemorrhage is also observed in scurvy, purpura, in 
some infectious diseases, such as typhoid fever, yellow fever, in poi- 
soning with phosphorus, etc. 

Since the formation of fibrin begins as soon as the blood has left 
its natural channels, it is apparent that absolutely accurate analyses 
of blood-plasma can hardly be expected. The appended analyses of 
the plasma of the horse's blood are taken from Hoppe-Seyler and 
Hammarsten, the figures having reference to 1000 parts : 



"Water . 

Solids . 

Total albumins 

Fibrin 

Globulin 

Serum-albumin 

Fat . 

Extractives 

Soluble salts 

Insoluble salts 



908.4 
91.6 
77.6 
10.1 



1.2 
4.0 

6.4 
1.7 



917.6 
82.4 
69.5 
6.5 
38.4 
26.4 

12.9 



The chief points of difference existing between plasma and serum 
are the absence of fibrinogen and the presence of traces of fibrino- 
globulin, as well as of large quantities of fibrin-ferment, in the latter. 

From the following table it will be seen that a marked difference 
exists in the nature of the mineral ingredients between serum and 
red corpuscles, the latter being relatively rich in potassium salts and 
phosphorus, and poor in sodium salts and chlorine. 



THE BLOOD. 25 

The figures have reference to 1000 parts of Mood : 

Man. Woman. 





Red rorpuscles. 


Serum. 


Red corpus 


Scrum. 


K 


. 1.586 


0.153 


1.112 


0.200 


Na,0 


. 0.241 


1.661 


0.648 


1.916 


CaO 










MgO 










' • 










CI . 


. 0.898 


1.722 


0.362 


1.44 


P.,0 5 . 


. 0.695 


0.071 


0.643 


2.202 



It is noteworthy that the amount of sodium chloride in the serum, 
6 to 7 p. in., remains fairly constant, whether large amounts of 
sodium chloride are ingested, or none given at all. It is quite prob- 
able that the sodium chloride of the plasma serves the purpose of 
preventing the haemoglobin of the corpuscles from being dissolved 
by the water of the blood. The term " isotonia " has been applied 
by Hamburger to a salt solution which is just strong enough to pre- 
vent the solvent action of the water upon the haemoglobin of the red 
corpuscles. In the case of the serum, however, we meet with a con- 
dition of hyperisotonia ; i. e., an amount of salt in excess of that 
actually required, in order to prevent the destruction of the red cor- 
puscles, the advantage of which is, of course, apparent, if the varia- 
tions to which the amount of water in the blood is subject be borne 
in mind. 

In addition to the substances mentioned, the following are also 
found in the blood : 

Fat occurs in an amount of from 1 to 7 p. m. in fasting animals, 
while following the ingestion of a meal rich in fats as much as 12.5 
p. m. has been encountered. 

Soaps, cholesterin, and lecithin have likewise been found. 

Sugar, probably glucose, appears to form a normal constituent of 
the plasma, amounting to 1 to 1.5 p. m. in man. While it is possi- 
ble to increase this amount to a certain degree by the ingestion of 
large quantities of sugar, this appears in the urine, accordiug to 
Claude Bernard, as soon as 3 p. m. has been exceeded. In addition 
to glucose another reducing substance has been found in the blood, 
which differs from the former in not being fermentable. 

Among the extractives which have been found there may be men- 
tioned : urea, uric acid, kreatin, carbarn ic acid, sarco-lactic acid, 
glycogen, and hippuric acid, and under pathologic conditions xan- 
thin, hypoxanthin, paraxanthin, adenine, guanine, leuciu, tyrosin, 



CLINICAL DIAGNL SIS 

lactic acid, cellulose - :: :iityrie acid, acetone, and biliary constit- 

It has been pointed out that the color of the blood is referable :: 
the presence of haemoglobin contained in the red corpuscles, and 
also that its color varies from a bright scarlet-red in the arteries to a 
dark bluish-red in the veins, the exact shade depending upon the 
amount of >xygen present in combination with haemoglobin, as oxy- 
hemoglobin. Upon chemical examination two other gases may be 
lemonstrated under physiologic conditions, viz.. carbon dioxide and 
nitrogen. Of these the latter appears to play no part in the body- 
economy, and the amount present merely corresponds to that which 
would be absorbed by an equal volume of distilled water, viz.. 1.8 

:.. p. c. . calculated at ~. : C. and ~. Hgmm. pressure. 

The amount of oxygen and carbou dioxide, on the other hand, 
undergoes considerable variation, depending upon the particular 
bloodvessel from which the specimen is taken — i. e. y whether this be 
an artery or a vein, and, furthermore, upon the velocity of the blood- 
current, the temperature of the body, rest, exercise, etc. 

The relation existing between the amounts of thesr gases in arteries 
reins :.:: y be seen from the following table : 

Arterial blood. Venous blood. 
Per cent. Per cent. 

: --^en 21.6 

. _ :I: :z:::e 40i 

Nitrogen 1.8 1.8 

Oxygen, as already pointed out. occurs principally in chemical 
combination with hemoglobin (oxyhemoglobin), only 0.26 percent, 
being present in solution in the plasma. 

Of the carbon dioxide which may be obtained from the blood, 
ne-tenth is held in solution, while the remaining portion is 
found in the red corpuscles, in the form of a loose compound with 
the alkalies of the corpuscles, and possibly also in combination 
with hemoglobin. This portion amounts to about one-third of the 
total quantity, while the remaining two-thirds are probably held in 
chemical combination by the alkalies of the plasma and certain albu- 
minous bodies. 

Blood-pigments . 
Haemoglobin. Hemoglobin as such is found in only relatively 
small amounts in the circulating: blood, occurring essentiallv in com- 
bination with oxygen as oxyhemoglobin, which predominates in 



THE BLOOD. 



27 



arterial blood, while a mixture of oxyhemoglobin and haemoglobin 
is met with in venous Mood, and haemoglobin almost exclusively in 
the blood oV asphyxia. 

The spectrum of haemoglobin, in suitable dilution, shows one sin- 
gle band of absorption between 7) and E, which, however, docs not 
lie midway between these lines, but extends slightly beyond J) toward 
the left (Fig. 1). The substance is characterized by the ease with 




Spectrum of reduced haemoglobin, (v. Jaksch.) 

which it forms compounds with certain gases, and notably so with 
oxygen. As has been stated above, carbon dioxide also, to a certain 
extent at least, occurs in combination with haemoglobin. In cases of 
poisoning compounds of haemoglobin with carbon monoxide, with 
nitric oxide, and possibly also with suphuretted hydrogen, cyanogen, 
and acetylene have been observed. 

Oxyhemoglobin. Oxyhemoglobin is the most important con- 
stituent of the blood. In sufficiently dilute solution it shows two 
bands of absorption between D and E ; one band, a, which is not 
so wide as the secoud, ,9, but darker and more sharply defined, bor- 
ders upon D, while the second which is wider, but less sharply 
defined, lies at E (Fig. 2). This spectrum can be readily trans- 



Cyanblue 




Eb F 

80 90 100 

ll l l ll.lllllllll ll lll 



Spectrum of oxyhemoglobin, (v. Jaksch.) 



formed into that of haemoglobin proper by the addition of a reduc- 
ing agent, such as an ammoniacal solution of ferrous tartrate (Stokes's 
fluid), ammonium sulphide, and cuprous salts. 

Under normal conditions the amount of oxyhemoglobin is fairly 



28 CLINICAL DIAGNOSIS. 

constant, while considerable variations are met with in disease. As 
the result of 61 estimations, Leichtenstern found 14.16 per cent, as 
the average in healthy men, 13.10 per cent, in women, and in old 
age about 95 to 115 per cent, of the normal. While the ingestion 
of large amounts of water does not call forth a dilution of the blood 
and a diminution in the amount of oxyhemoglobin, an increase occurs 
upon the withdrawal of liquids. Fat persons, furthermore, show 
a smaller amount of oxyhemoglobin than corresponds to their age. 

A great diminution in the amount of oxyhemoglobin may be en- 
countered under pathologic conditions, and especially in chlorosis, 
while a relative increase is not infrequently met with in diabetes 
mellitus, owing to the excretion of abnormally large quantities of 
water. In nephritis with pronounced cedema it falls considerably 
below the normal. 

In a series of observations Quincke found the following amounts 
in the diseases indicated : 







FleischU 


Angina pectoris . 


. 14.4 per cent. 


107.0 


Cerebral apoplexy 


. 14.1 


104.9 


Scurvy .... 


. 14.6 


108.6 


Hepatic cirrhosis . 


. 10.1 


75.1 


Chlorosis 


5.32-9.92 


39.5-73.9 


Splenic leukaemia . 


5.8 


43.1 


Nephritis 


8.5-10.7 


63.2-79.6 


Diabetes 


. 14.4-15.9 


107.1-118.3 


Typhoid fever 


. 12.7-14.6 


94.4-108.6 


Eecurrens 


. 14.4 


107.0 


Meningitis . 


. 15.0 


111.6 


Pyaemia 


. 11.3 


84.0 


Phosphorus-poisoning . 


. 14.9 


110.8 



In an analysis of 63 cases of chlorosis, observed at the Johns Hop- 
kins Hospital, an average amount of 5.68 per cent. (42.3 Fleischl), 
with a minimum of 2.35 per cent. (17.5) was observed, chlorosis thus 
occupying the foremost position among the various pathologic condi- 
tions associated with oligochromaemia. Very low figures are also seen 
in cases of pernicious anaemia and leukaemia, where 2.68 per cent, i 20 
Fleischl) and 4.36 per cent. (32.5), respectively, were obtained. 

T\ bile in typhoid fever the amount of oxyhemoglobin is always 
reduced, according to Osier, and usually in a greater relative propor- 
tion than the number of red corpuscles, the most severe grades of 
anaemia may here be encountered during convalescence, when the 

1 See estimation of haemoglobin with Fleischl's hsemometer, p. 29. 



THE BLOOD. 29 

amount of oxyhemoglobin may fall as low as 2.68 per cent. (20 
Fleischl). 

An oligochromasia of considerable intensity also occurs in vari- 
ous diseases of the stomach, notably in carcinoma, as also in chronic 
lead and mercurial poisoning, tuberculosis, syphilis, etc. 

As the oxyhemoglobin is contained in the bodies oi' the red cor- 
puscles it might be inferred that the amount of the former will directly 
depend upon the number of the latter, so that the degree oi' an anae- 
mia could be determined by an enumeration of the red corpuscles as 
well as by a direct estimation of the amount of oxyhemoglobin. 

While this rule holds good generally, there are numerous excep- 
tions which go to show that a diminution in the amount of oxyhe- 
moglobin, viz., an oUc/ochromcemia, is not necessarily accompanied by 
a corresponding diminution in the number of red corpuscles, i. e., 
an oligoeythcemia. In chlorosis, for example, the red corpuscles may 
be present in normal numbers, while the amount of oxyhemoglobin 
is greatly diminished. Here, it is true, a well-defined oligocythe- 
mia simultaneously occurs in all severe cases, but even then the 
oligochromemia exceeds the oligocythemia. Conversely in perni- 
cious anemia the oligocythemia, while accompanied by an oligochro- 
memia, quite constantly exceeds the latter. 

It is thus clear that definite inferences regarding the amount of 
hemoglobin cannot be drawn from an enumeration of the red cor- 
puscles, and vice versa. 

While it is generally possible to form a fairly clear idea of the 
degree of an anemia by inspection — i. e., by noting the " color" of 
a patient — it is a well-known fact that not every pale face denotes an 
anemic condition. Whenever special accuracy in examination or 
results for comparison are desired, recourse should hence be had to in- 
struments especially devised for the purpose of determining the amount 
of hemoglobin, known as hemoglobinometers or hemometers. 

Among these instruments that devised by Fleischl is undoubtedly 
the most convenient and has already largely replaced the older forms 
of Gowers, Malassez, and Hay em. 

ESTIMATION OF HAEMOGLOBIN WITH FLEISCHI/'s H.EMOMETER. 

The principle of the method depends upon the comparison of the 
color of the blood, diluted with water, with that of a glass wedge, 
stained with the golden purple of Cassius or a similar pigment. 

The instrument (Fig. 3) essentially consists of the glass wedge, 
just mentioned, to which a scale is attached, ranging from to 120, 



30 



CLINICAL DIAGNOSIS. 



being placed at the thinnest, 120 at the thickest portion of 
the wedge. This, by means of a rack and pinion, can be made 
to slide from side to side beneath a platform corresponding to the 
stage of the microscope. In the centre of the platform there is 
a circular opening into which artificial light (daylight is not permis- 
sible) is projected from a circular plate of plaster-of-Paris, mounted 
beneath, in the position of the mirror of a microscope. Into the 
circular opening a metallic tube, 1.5 cm. in height, closed at the bot- 



Fig. 3. 




Von Fleischl's hairnoineter. 



torn with a plate of glass, and divided into two equal compartments 
by a metal partition, is fixed. One compartment receives the light 
through the glass wedge, the red chamber, the other directly from 
the plaster-of-Paris reflector, the white chamber. 

Capillary pipettes of such a capacity that, if the blood of a per- 
fectly normal individual be used, the mixture of blood and water, 
placed in the compartment receiving light directly from the white 
plate, shall correspond in color to that derived from the colored wedge 



THE BLOOD. ,;i 

at the mark 100, accompany the instrument. The two compart- 
ments are partially filled with water, when the required amount of 
blood is obtained by placing one end of a capillary pipette in contact 
with a drop of blood, obtained from the tip of a finger, or, si ill better, 
from the lobe of an ear that has been carefully cleansed with water, 
alcohol, and finally with ether. The pipette is immersed in the white 
chamber and rotated between two fingers, when the blood will pass 
into the water, which latter dissolves out the haemoglobin from the cor- 
puscles. Any trace of blood remaining in the pipette is carefully 
washed out with water, an ordinary medicine-dropper being used for 
the purpose. By means of the dropper the two compartments are 
then completely filled with water until a convex meniscus is obtained 
over the two chambers. A slip of paper is placed over the visible 
portion of the scale on the surface of the platform, immediately 
behind the well, and the glass wedge so adjusted by means of the 
screw that the color in the two chambers shall be the same. The 
number facing the uotch in the scale-aperture of the platform will 
then indicate the percentage of haemoglobin, that of a healthy indi- 
vidual correspouding to 100. 

As the normal amount of haemoglobin contained iu 100 grammes 
of blood is a little less than 14 grammes, the number 100 on the scale 
of Fleischl's instrument correspouding to 13.7 per cent., the percent- 
age in a given specimen may be calculated according to the equa- 

pl3.7 , 

tiou : 100 : 13.7 : : p : x, and x = , ~~ ,where p represents the 

reading on the scale and x the corresponding amount of haemoglobin, 
contained in 100 grammes of blood. 

According to Dehio, certain errors are incurred in the estimation 
of haemoglobin by means of Fleischl's haemometer, which become the 
more marked the smaller thepercentage of haemoglobin. According to 
the same observer, these may be obviated, however, aud accurate re- 
sults obtained, as far as such is possible, with the employment of colori- 
metric methods, if the instrument is previously tested with a solution 
of blood, the color of which accurately coincides with that of the wedge 
at the 100 mark. To this end the standard solution is diluted with 
from 10 to 90 volumes of water, and any difference that may exist 
in the readings of the instrument, as compared with the known per- 
centages, noted. 

If the number of red corpuscles be known, the amount of haemo- 
globin contained in each, " la valeur globulaire " of Lepine, can now 



- 



1UNICAL DIAGNOSIS. 



be readily determined, a point of considerable importance in differ- 
ential diagnosis 

EsmMATIOX OF H yjJOGLOBCs WITH GOWEBS'S Hmmoguobi- 
: ::zrz7 G wers 3 - asemoglobinomefer is much cheaper than that 
of Fleischl and yields results which compare favorably with those 
obtained with the latter instrument. The apparatus (Fig. 4) consists 
of : a closed tnbe (D), containing a solution of picrocarmine-glycerine, 
the color of which corresponds to a 1 per cent, solution of normal 
blood ; a similar tube (C), about 11 cm. in height, provided with 
an ascending scale of 134 divisions, each corresponding to 20 cbmm. ; 
a capillary pipette (B), marked at 20 cbmm. ; a guarded lancet (F) ; 
and a dropping-bottle with rubber top (A). 






I-:-er= • 



In order to estimate the relative amount of haemoglobin in a given 
case the tip of a finger, or, still better, the lobe of the ear, is freely 
punctured, after having been carefully cleansed, as described above, 
and the pipette filled with blood to the 20 cbmm. mark by suction. 
Any trace of blood that may adhere to the outer surface of the pipette 
iref ully wiped off, and the contents at once mixed with a few 
drops of distilled water, previously placed in the graduated tube, so 
as to guard against the blood coagulating on its walls. In order to 
make the error incurred, when this method is employed, as small 
as possible, care should be had to remove completely every trace of 
blood from the interior of the pipette, by refilling the same with 






THE BLOOD. 33 

distilled water, and blowing the contents into the graduated tube. 
The two tubes are then held side by side, directly against the Light, 

or against a sheet of white paper, when water is added, while shak- 
ing, drop by drop, until the shade of color is the same in the two 
tubes. The division on the scale ultimately reached will express the 
relative percentage of haemoglobin. 

Hjemoglobinjemia. The term hemoglobinemia has been applied 
to a condition in which, as the result oi' abnormal influences, the haemo- 
globin is dissolved out from the red corpuscles, and, appearing in 
the plasma as such, leads at first to a very decided choluria and in 
extreme cases to haemoglobin uria. 

Various poisons, such as potassium chlorate, carbolic acid, pyro- 
gallic acid, naphthol, arsenic, sulphide 01 antimony, muriatic acid, 
sulphuric acid, autifebrin, antipyrin, phenacetin, sulphonal, tincture 
of iodine, when given hypodermically, or even internally in suffici- 
ently large doses, will call forth a hemoglobinemia, followed by 
hemoglobinuria. 

Fresh morels also contain a poison which is capable of producing an 
intense hemoglobinuria, and which may be extracted with hot water. 

In acute and chronic infectious diseases of a severe type, such as 
scarlatina, typhoid fever, intermittent fever, icterus gravis, syphilis, 
as also in diseases depending upon a hemorrhagic diathesis, such as 
variola hemorrhagica, scurvy, as also following insolation, extensive 
burns, and frostbite, heinoglobinemia, leading to hemoglobinuria, 
is not infrequently observed. 

An epidemic hemoglobinuria of the newly born and a paroxysmal 
or intermittent hemoglobinuria, both of unknown origin, have like- 
wise been described. 

In one case of Raynaud's disease which the author had occasion 
to observe in the clinic of Dr. H. M. Thomas, at the Johns Hopkins 
Hospital, hemoglobinuria at times followed epileptiform seizures. 

Finally, hemoglobinemia followed by hemoglobinuria is observed 
after transfusion of the blood of one mammal into the circulation 
of another. 

In some cases, and particularly in those following poisoning witli 
chlorates, etc., the hemoglobinemia ultimately leads to a well-pro- 
nounced methemoglobinemia (see below). 

A hemoglobinemia, aside from a urinary examination, may be 
readily recognized by a spectroscopic examination of the serum, when 
the two bands of absorption of oxyhemoglobin will be observed. 



34 



CLINICAL DIAGNOSIS. 



A very simple method which may be employed for the same pur- 
pose is the following : A small amount of blood is drawn from the 
patient by means of cupping-glasses and immediately placed on ice, 
where it is allowed to remain from twenty to twenty-four hours. At 
the expiration of this time the clot formed will have shrunk, float- 
ing if the blood be normal in the clear, straw-colored serum, while a 
beautiful ruby-red color is obtained in cases of haemoglobinaemia. 
If, furthermore, some of this serum be heated to a temperature of 
from 70° to 80° C, the coagulum in the presence of haemoglobin 
will present a more or less deep brown color. 

Carbon Monoxide Haemoglobin. In cases of coal-gas poison- 
ing the blood, both of arteries and veins, presents a bright cherry- 
red color, owing to the presence of carbon monoxide haemoglobin. 

Such blood when properly diluted, like oxyhemoglobin, shows two 
bands of absorption between D and E (Fig. 5), which are nearer the 



Fig. 5. 



Eed Orange 



Yellow 



Green 



Cyanblue 



A a B C 

10 50 

iiiliiiil,ni)l,iiiiliinliii 




Eb F 

80 90 100 110 

lllllllllllll l llljllllll ll lll l ll 



Spectrum of carbon monoxide haemoglobin, (v. Jaksch.) 



violet end of the spectrum, however, and may be readily distin- 
guished from those referable to oxyhaemoglobin by the addition of a 
reducing agent. This will not affect the spectrum of carbon monox- 
ide haemoglobin, while that of oxyhaemoglobin is transformed into 
the spectrum of reduced haemoglobin. 

For medico-legal purposes a number of additional tests have been 
devised, among which that suggested by Hoppe-Seyler is one of the 
simplest, and at the same time most reliable. The blood is treated 
with double its own volume of a solution of sodium hydrate (sp. gr. 
1.3). Normal blood is thus changed into a dirty-brownish mass, 
which, when spread out upon a porcelain plate, exhibits a trace of 
green, while carbon monoxide blood yields a beautiful red under the 
same conditions. 

Nitric Oxide Hsemog-lobin. The blood in cases of poisoning 
with nitric oxide, owing to the presence of nitric oxide haemoglobin, 
yields a spectrum which is similar to that of carbon monoxide haemo- 



THE BLOOD. 35 

globin,the bands, however, being less sharply defined and paler than 

those of the latter, and which, like these, do not disappear upon the 
addition ol a reducing Bubstance. 

Sulphuretted Hydrogen Haemoglobin (Methaemoglobin Sul- 
phide). In cases of poisoning with sulphuretted hydrogen, notwith- 
standing the researches of Hoppe-Seyler, which go to show that 
haemoglobin will enter into combination with this gas, no definite 
changes can be discovered in the blood upon spectroscopic exam- 
ination. It is stated, however, that in such cases the blood becomes 
dark and o\ a dull greenish tint, the distinction between arterial and 
venous blood being at the same time lost. 

Carbon Dioxide Haemoglobin. With carbon dioxide, as men- 
tioned above, haemoglobin is also thought to enter into combination, 
the spectrum being similar to that of reduced haemoglobin. The 
latter, in fact, is formed artificially when carbon dioxide is passed 
through a solution of oxyhemoglobin. If this process be carried 
farther, hemoglobin is decomposed, a precipitate of globulin being 
thrown down, and an absorption-band obtained which is similar to 
that resulting when hemoglobin is decomposed with acids (see below). 
The question has hence arisen whether the so-called carbon dioxide 
hemoglobin spectrum is not in reality referable to carbon monoxide 
hemochromogen, the hemochromogen, according to Hoppe-Seyler, 
being the colored portion of the hemoglobin and its compounds with 
gases. 

The blood-changes occurring in cases of poisoning with hydro- 
cyanic acid and acetylene are as yet but little known, and the reader 
is referred to special works upon toxicology for their consideration. 

Haematin. If hemoglobin in aqueous solution be heated to a 
temperature of from 60° to 70° C, it is decomposed into an albu- 
minous body, belonging, in all probability, to the class of globulins, 
and hematin. The same result is also reached by treating the aque- 
ous solution with acids, alkalies, or the salts of various heavy metals. 

Hematin is an amorphous, blackish-brown or bluish-black sub- 
stance which is frequently encountered in old transudates, in the 
stools after hemorrhages, and after meals rich in meats — 1. e., blood. 
It is said to occur in the urine in cases of poisoning with arsenic, 
and in the blood of animals poisoned with nitrobenzol the presence of 
this body is likewise said to be demonstrable with the spectroscope. 

In acid solutions it shows a well-defined spectral band between C 
and D (Fig. 8). Between D and Fa second band is seen, which is 



36 



CLINICAL DIAGNOSIS. 



much wider, but less sharply defined than the first, and may be re- 
solved into two bands by dilution, one between b and F y near F, and 
another between D and E, near E ; a fourth faint band, finally, may 
be obtained between D and E, near D. As a rule, only the band 
between C and D, and the broad band, viz., the two bands between 
D and F, are seen. 

An alkaline solution, on the other hand, shows but one broad 
band,: the greater portion of which lies between C and D, extending 
slightly beyond D (Fig. 6). 



Fig. 



Red Orange 
A a 



Yelloic 



Green 



Cyariblne 




Spectrum of hsematin in alkaline solution, (v. Jaksch.) 
Fig. 7. 



Bed Orange Yellow 



Green 



Cyanblue 




Spectrum of reduced hse matin, (v. Jaksch 



If an alkaline solution of haarnatin is treated with a reducing 
substance, reduced hsematin results, which gives rise to two bands 
of absorption between D and E (Fig. 7). 

Heemin. Hsematin readily combines with one molecule of muri- 
atic acid to form haaroin. This substance crystallizes in light or 
dark brown rhombic plates or columns, which are highly character- 
istic (Plate I., Fig. 1). They bear the name of their discoverer, 
Teichmann. The size of these crystals varies with the manner in 
which they are produced, the largest specimens being encountered 
when the glacial acetic acid (see below) is allowed to evaporate as 
slowly as possible. Specimens measuring from 15 p. to 18 p in length 
may thus be seen. Smaller crystals will at the same time be present, 
occurring either singly or gathered in stars, rosettes, and crosses. 
As these may be obtained from mere traces of blood, their formation 
must be regarded as conclusive evidence in medico-legal examinations. 



PLATE I 



FIG. 1 



*L A 

Crystals of Haemin. (Highly magnified.) 



FIG. 2. 



If ^ ^.>* 




eP 






•/ 






Crystals of Haematoidiu from au Alcoholic Stool, 
iv. Jaksch.j 



THE 11LQ0D. 



37 



Method, A small drop of normal salt-solution is carefully evap- 
orated upon a slide, when a few particles of the suspected material, 
powdered or teased as finely as possible, are placed upon the deli- 
cate layer of crystallized salt. The preparation is covered with a 
cover-glass, and glacial acetic acid allowed just to fill the space be- 
tween the two glasses. The specimen is then carefully heated (three- 
quarters to one minute) until hubbies oi' gas begin to form beneath 
the cover. While evaporation is being continued glacial acetic acid 
is further added, drop by drop, from the edge of the slip, until a 
faint reddish-brown tint appears. As soon as this point is reached, 
the last traces of the acid are allowed to evaporate, the specimen 
being held at a greater distauce from the flame. A drop of glycerin 
is finally added, when the preparation may be examined under the 
microscope, attention being directed especially to any reddish-brown 
streaks or specks, which, in the presence of blood, can usually be 
made out with the naked eye. 

Methaemog-lobin. Methemoglobin is a pigment closely related 
to oxyhemoglobin, and is frequently encountered in sanguinous trans- 
udates, cystic fluids, and in the urine in cases of hematuria and 
hemoglobinuria. In the circulating blood methemoglobin is found 
after the ingestion of large quantities of potassium chlorate, notably 
so in children, as also after the inhalation of nitrite of amyl, the 
use of kairin, thallin, hydrochiuon, pyrocatechin, iodine, bromine, 
turpentine, ether, perosmic acid, permanganate of potassium, and 
antifebrin. (See Hernoglobinemia, p. 33.) 



Fig. 



Bed Oranye Yellow 



Gre< n 



Cyanblue 







Spectrum of methtenioglobin in acid and neutral solutions, (v. Jaksch.) 



The spectrum of an aqueous or slightly acidified solution of methaB- 
moglobin (Fig. 8) closely resembles that of an acid solution of hema- 
tin, but differs from the latter by the ease with which it is trans- 
formed into that of hemoglobin upon the addition of an alkali and 
a reducing substance. The spectrum of hematin under the same 
conditions is transformd into that of an alkaline solution of hemo- 



38 



CLINICAL DIAGNOSIS, 



chromogen. In alkaline solutions, on the other hand, two bands of 
absorption are observed, which are similar to those of oxyhemoglo- 
bin, but differ from these by the fact that the band nearer E, /3, is 
more pronounced than the one at D, a. A third, but very faint 
band, may, furthermore, be observed between C and D, near D. 

Haematoidin. Small amorphous particles of an orange or ruby- 
red color, or crystals belonging to the rhombic system (Plate I., Fig. 
2), occurring either singly or in groups, are frequently met with in 
the sputum, the urine, and the feces, as well as in old extravasations 
of blood. These were first discovered by Virchow, who applied the 
term hsematoidin to this particular pigment, the hemic origin of 
which is undoubted, being probably derived from hsematin. 

Heematoporphyrin. Hsematoporphyrin is likewise a derivative 
of hsematin, and, according to Nencki and Sieber, isomeric with bil- 
irubin. In dilute solution with sodium carbonate it shows four bands 
of absorption, one between C and D, a second one, broader than the 
first, about D, especially marked between D and E, a third one, not 
so broad and less sharply defined between D and E, and a fourth 
one, broad and dark, between b and F (Fig. 9). 



Red Orange 



Cyanblue 




Spectrum of heematoporphyrin in alkaline solution. 

The clinical significance of this body, which also appears in the 
urine under certain conditions, as well as the causes giving rise to its 
formation, are as yet unknown. (See Hsematoporphyrinuria.) 

While it is possible, as pointed out above, to recognize definitely 
the presence of blood by the hsemin-test, recourse should always be 
had to spectroscopic examination whenever the exact nature of the 
pigment under consideration is to be determined. 

The Spectroscope. The spectroscope (Fig. 10) essentially con- 
sists of a tube (A), provided with a slit at its distal end which may be 
narrowed or widened, and a collecting-lens at its proximal end. 
Through the latter rays of sunlight or of artificial light are thrown 
upon a prism (P), where they are decomposed into a colored spectrum 



► OD. 



39 



which is viewed through an astronomical telescope (B). Through a 
third tube(C) a tine scale, illuminated by artificial light, is reflected 
by the prism to the eye of the observer, appearing immediately above 
the colored spectrum, the left end of which is red, passing into yellow, 

this into green, then into bine, indigo, and finally into violet, which 
occupies the right end. These colors, however, are not continuous, 
but are interrupted by a large number of vertically placed dark 
lines, named after Fraunhofer. The most marked of these he 



Fig. 10. 




Spectroscope. (Xeubauer.) 



designated by the letters : A, a, B, C y I), E, b, F, G, and H. Of 
these, A is found at the left end and B in the middle of the red por- 
tion of the spectrum, C at the boundary of the red and the orange, 
D in the yellow, E in the green, F in the blue, G in the indigo, and 
iJin the violet portion ; a is situated in the red between A and B, 
nearer A, and b in the green between E and F, nearer E. 

If now a colored medium be placed between the slit and the light, 
not all the rays of colored light reach the eye, but some become 
absorbed. In the case of blood, for example, it may thus be seen 
that a portion of the yellow and a portion of the red rays are 



40 CLINICAL DIAGNOSIS. 

absorbed, a spectrum of this kind being spoken of as an absorption- 
spectrum. 

For clinical purposes various instruments, modifications of the 
one described, have been devised, among which those of Desego of 
Heidelberg, Zeiss of Jena (Fig. 11), and Hoffmann of Paris, as 

Fig. 11. 




Browning's spectroscope. (Zeiss.) 



well as Hering's lenseless spectroscope, and Henocque's instrument, 
the latter two, owing to their cheapness particularly, deserve especial 
mention. 

THE PROTEIDS OF THE BLOOD. 

In considering the proteids of the blood from a clinical point of 
view, it is necessary to distinguish between an increase and a diminu- 
tion in their normal amount, constituting the conditions of hyper- 
albuminosis and hypalbuminosis, respectively. As may be expected, 
the former is met with whenever water is more rapidly withdrawn 
from the system than it can be supplied, and is hence observed in 
cases of cholera, acute diarrhcea, following the use of purgatives, etc. 
This increase in the amount of proteids is only a relative increase, 
the occurrence of an absolute increase not having as yet been satis- 
factorily demonstrated. An absolute hypalbuminosis, on the other 
hand, is observed following a direct loss of proteids from the blood, 
as in hemorrhage, dysentery, albuminuria of high degree, the forma- 
tion of large collections of pus, etc. This is generally associated with 
a relative increase in the amount of water — i. <?., a hydremia, which 
is particularly noticeable after hemorrhages, and referable to a dimin- 
ished secretion and excretion of water, as well as a direct absorp- 
tion of the same from the tissues. 

The term hyperinosis has been applied to a condition in which the 




THE BLOOD. 41 

amount of fibrin is increased, and is said to occur in various inflam- 
matory diseases, such as pneumonia, acute articular rheumatism, and 
erysipelas, while a diminished amount of fibrin, hypinosis, has been 
observed in malaria, pyaemia, and pernicious anaemia. 

In order to determine the amount of fibrin, 30 to 40c.c. of blood, 
obtained by means of cupping-glasses, are placed in a previously 
weighed beaker, fitted with an India-rubber cap, through the centre 
of which passes a piece of whalebone, firmly fixed. The blood is de- 
fibrinated by beating with the whalebone, and the beaker with its 
contents is weighed, the difference indicating the weight of the 
blood. The beaker is then filled with water and the mixture again 
beaten, whereupon the fibriu is allowed to settle ; after being washed 
with normal salt-solution, it is filtered through a filter of known 
weight, further washed with normal salt-solution, until free from 
coloring-matter, then boiled in alcohol to dissolve out the fat, choles- 
terin, and lecithin, dried at 110° to 120° C.,and weighed upon cool- 
ing over sulphuric acid. 

In leukemic blood von Jaksch was able to demonstrate peptones 
in considerable quantities, and especially so after death, when the 
amount progressively increased as decomposition advanced. Matthes, 
on the other hand, could detect no true peptones, but found that the 
blood contained a deuteroalbumose. In one case the serum contained 
an abundance of nucleoalbumin, derived in all probability from de- 
generated leucocytes. 

In order to test for peptones in the blood, all other proteids should 
first be removed by salting with ammonium sulphate and heating, as 
will be described in detail later on, when a positive biuret-reaction in 
the filtrate may be regarded as indicating the presence of peptones. 

Carbohydrates. 

Sugar. Sugar, as indicated above, occurs normally in the blood, its 
quantity varying between 1 and 1.5 p. m. Under pathologic condi- 
tions this amount may be exceeded by far, and notably so in diabetes, 
in which Hoppe-Seyler found as much as 9 p. m. in a certain case. 

In addition to sugar a non-fermentable reducing substance has been 
encountered in the blood, the exact nature of which is still unknown. 

Large quantities of a reducing substance, the greater portion of* 
which consisted of sugar, have been met with by Trinkler in carci- 
noma ; it was observed at the same time that carcinoma of the inter- 
nal organs was associated with far greater amounts of sugar than 



42 CLINICAL DIAGNOSIS. 

cancerous disease of the skin and the mucous membranes. It is 
also interesting to note in this connection that an increase in the 
degree of the cachexia was not accompanied by an increase in the per- 
centage of sugar. 

The results reached apparently bear out the correctness of the con- 
clusions formed by Freund, who claimed that a differential diagnosis 
between carcinoma and sarcoma, in which latter condition no increase 
in the amount of sugar was noted, can always be effected upon the 
basis of an examination of the blood in this direction. 

In the following table the percentages found in the different dis- 
eases investigated are given, from which it is apparent that next to 
carcinoma the largest quantities of sugar are met with in the infectious 
diseases and the lowest figures in diseases of the kidneys : 





Average. 


Minimum. 


Maximum 




Per cent. 


Per cent. 


Per cent. 


Carcinoma 


. 0.1819 


0.1023 


0.3030 


Typhoid fever . 


. 0.0950 


0.0875 


0.1022 


Pneumonia 


. 0.0943 


0.0813 


0.1092 


Dysentery 


. 0.0838 


0.0796 


0.0915 


Vitium cordis . 


. 0.0737 


0.0664 


0.0897 


Peritonitis 


. 0.0701 


0.0450 


0.0917 


Tuberculosis . 


. 0.0653 


0.0450 


0.0817 


Syphilis . 


. 0.0553 


0.0449 


0.0748 



Nephritis and uraemia . 0.0489 0.0321 0.0559 

In order to demonstrate sugar in the blood the proteids are first 
removed by boiling with an equivalent weight of sodium sulphate, 
when the various tests for sugar, to be described later on, may be 
applied to the filtrate, and its quantity estimated as there indicated. 

G-ly cog-en. There appears to be no doubt that glycogen normally 
occurs in the blood of various animals. Huppert, in fact, succeeded 
in demonstrating its presence in all animals examined, the amount 
varying between 0.114 and 1.560 grammes for a hundred parts 
of blood. Czerny, on the other hand, was not able to confirm 
these results in the blood of healthy adults, while in sick children 
an examination of the leucocytes furnished positive results, glycogen 
being met with — in chronic gastro-intestinal diseases, pneumonia, 
anaemia, furunculosis, cachectic conditions, the result of tubercular 
disease, asphyxia, etc. In diabetes and leukaemia also the glycogen- 
reaction is said to be quite pronounced. 

In order to test for glycogen a drop of blood is carefully spread 
out between two cover-slips and dried at an ordinary temperature, 



THE BLOOD. 43 

when a drop oi a solution composed of 1 gramme oi iodine and 3 
grammes oi' potassium iodide in 100 grammes of concentrated muci- 
lage is allowed to flow between the two preparations. In the pres- 
ence of glycogen brown-colored granules will be observed occurring 
free in the blood, or contained in the so-called neutrophilic leuco- 
cytes. 

Cellulose. Cellulose has been found in the blood of tubercular 
patients. 

Urea. 

Urea normally occurs in the blood in traces, 0.016 to 0.020 per 
cent., larger amounts being encountered whenever for any reason, 
as in nephritis, various diseases of the urinary organs, cholera Asi- 
atica, cholera infantum, eclampsia, etc., its elimination is impeded, or 
whenever, as in fever, owing to increased albuminous decomposition, 
urea is formed in abnormally large quantities. 

In this connection it is interesting to note that a smaller amount 
of urea is found in fatal cases of eclampsia than in those ending in 
recovery, an observation which has been explained by the assump- 
tion that in the former condition not only the kidneys, but also the 
liver loses its functional activity. 

The methods which are available for the detection of urea in the 
blood are still too complicated for clinical purposes, and the value of 
the information derived so small as hardly to repay for the labor 
involved. Hoppe-Seyler's method should be employed whenever 
an examination in this direction is deemed advisable. 1 

Uraemia. Formerly it was thought that the complex of symp- 
toms generally spoken of as uraemia was referable to the retention 
in the blood of urea, or ammonium carbonate, a view which has since 
been disproved, although it must be admitted that in this condition 
au increased amount of urea is frequently noted. Other views, 
according to which the ursemia is referable to an accumulation of 
potassium salts, of extractives, or of ptomaines in the blood, must 
still be regarded as being sub judice. There is no reason, however, 
to ascribe the urrernic condition to the retention in the blood of one 
particular constituent of the urine, and it is not at all improbable 
that a retention of all may be responsible for the symptoms observed. 

1 See Hoppe-Seyler : Handbuch des physiologisch- und pathologisch-chemischen Analyse. 
Vierte Auflage, p. 363. 



44 CLINICAL DIAGNOSIS. 

Uric Acid and the Xanthin-bases. 

Uric Acid. Formerly, the presence of appreciable amounts of 
uric acid in the blood was regarded as fairly pathognomonic of gout. 

Since that time a definite lithsemia has been observed in a variety 
of disorders, such as pneumonia, acute and chronic nephritis, chronic 
gastritis, catarrhal angina, conditions associated with an insufficient 
aeration of the blood, as in the various diseases of the heart, pleurisy 
with exudation, emphysema when accompanied by cyanosis, the 
severer forms of anaemia, etc. Fever in itself does not appear to 
lead to an increased production of uric acid, as negative results were 
obtained in nine cases of typhoid fever out of eleven, in five cases of 
acute articular rheumatism out of six, etc. The conclusion is thus 
forced upon us that the diminished alkalinity of the blood observed 
in nephritis and anaemia is, to some extent at least, dependent upon 
the presence of a nitrogenous acid, while the diminished alkalinity 
of the blood observed in fevers is not referable to this cause. 

From a survey of the literature upon the subject it would appear 
that an increased elimination of uric acid in the urine is not neces- 
sarily accompanied by an increase in the amount of uric acid in the 
blood. Further researches in this direction are, however, highly 
desirable, and particularly so in connection with the various forms of 
gastric disease, in which an increased elimination of uric acid, accord- 
ing to the author's experience, is so frequently observed. 

In order to test for uric acid in the blood the following rhethod 
may be employed : 100 to 300 c.c. of blood, obtained by means of 
cupping-glasses, are at once diluted with three to four times their own 
volume of water and placed upon a water-bath. As soon as coag- 
ulation sets in a few drops of a 0. 3 to 0. 5 per cent, solution of acetic 
acid are added, until a feebly acid reaction is obtained. After having 
been kept upon the boiling- water bath from fifteen to twenty minutes 
longer, until the albumin has separated out and settled in brownish 
flakes, the mixture is filtered while hot, and the precipitate washed re- 
peatedly with hot water. Filtrate and washings, which usually pre- 
sent a slightly yellow or brownish color, are again brought to the boil- 
ing-point after the addition of 0.3 to 0.5 per cent, of acetic acid, 
decanted, filtered, and after the addition of a small amount of disodic 
phosphate further treated according to the Ludwig - Salkowsky 
method (see Urine). The first filtrate is then treated with muri- 
atic acid, evaporated to about 10 c.c. and allowed to stand for twenty- 



Tin: BLOOD, 45 

four hours, when the uric acid that has separated out is filtered ofl 
through asbestos or glass-wool. The filtrate may then be examined 
Tor xan thin-bases according to the same method. If no uric acid 
crystallizes out, as not infrequently occurs, the muriatic-acid-eontain- 
ing fluid is directly examined for uric acid by means of the murexide- 
test (which see). If upon the addition of ammonia no distinct red 
color develops, the residue, after thorough desiccation, is dissolved 
in water, when a reddish color may be regarded as indicating the 
presence of uric acid, while a yellow or brown color is referable to 
certain xan thin-bases. 

G-arrod's Test : This test may be very advantageously employed if 
it be merely desired to determine whether or not large amounts of 
uric acid be present in the blood. A few c.c, of blood-serum (5-10) 
or of serous fluid, obtained by means of a blister, are placed in a 
watch-crystal and treated with from 6 to 10 drops of a 30 per cent, 
solution of acetic acid. A thread of linen is immersed in the fluid, 
which is then kept at a low temperature for from twelve to twenty- 
four hours. At the expiration of this time a few uric-acid crystals 
will have separated out upon the thread if the substance be present 
in large amounts. The true nature of these crystals may then be 
further determined by the microscope and the murexide-test. (See 
Uric Acid in the Urine.) 

Xanthin-bases. Xanthin-bases, as pointed out before, do not 
occur in normal blood, but have been encountered under pathologic 
conditions, as in typhoid fever, lymphatic tuberculosis, emphysema, 
phthisis pulmonalis, pleurisy, and chronic nephritis. 

The method above indicated for the demonstration of uric acid in 
the blood should also be employed when it is found desirable to test 
for these bodies. (See Urine.) 

Fat and Patty Acids. 

An increase in the amount of fat normally present in the blood, 
aside from that arising after the ingestion of large amounts of fatty 
food, is met with in cases of obesity, chronic alcoholism, injuries 
affecting the long bones, as also in severe cases of diabetes, various 
hepatic diseases, chronic nephritis, tuberculosis, malaria, cholera, etc. 
This increase constitutes the condition spoken of as lipannia. The 
term lipacidcemia has been applied to the occurrence of volatile fatty 
acids in the blood, noted by von Jaksch in various febrile diseases, 
leukaemia, and at times in diabetes, in which this condition is sup- 



46 CLINICAL DIAGNOSIS. 

posed to stand in a causative relation to the coma. /3-oxybutyric 
acid has been found post mortem in the blood in diabetes. 

To test for fat in the blood it is only necessary to examine a drop 
of the same microscopically for the presence of minute, highly re- 
fractive globules which are readily soluble in ether. 

To test for fatty acids 20 to 30c.c. of blood, obtained by means of 
cupping-glasses, are treated with an equivalent weight of sodium 
sulphate and boiled. The nitrate is then evaporated to dryness and 
extracted with absolute alcohol. Upon evaporation of this solution 
fatty acid crystals will be obtained, which can be readily recognized 
with the microscope. (See Feces.) 

Lactic Acid. 

There appears to be some doubt whether or not lactic acid normally 
occurs in the blood of man during life, while after death its presence 
appears to be constant, the amount determined as zinc lactate vary- 
ing between 0.233 and 6.575 p. m. In the series of cases studied by 
Irisawa it was impossible to account for the great variations observed 
in the amount of lactic acid by the character of the disease causing 
the fatal termination, and it is possible that the cause therefore lies in 
the fact that in some cases the blood was obtained shortly after death, 
while in others many hours had elapsed, as Irisawa himself suggests. 

The method employed by him is the following : 100 to 300 c.c. of 
blood are extracted with three times their own volume of alcohol, 
filtered, and the filtrate evaporated to a syrupy consistence. This is 
then made strongly alkaline with barium hydrate and shaken with 
large quantities of ether, in order to remove the fats present. The 
residue is acidified with phosphoric acid and again shaken with ether 
for twenty minutes at a time, until the process has been repeated five 
or six times, the lactic acid passing over into the ether. The ether 
is then distilled off from the extract, the residue taken up with water, 
and the solution carefully evaporated, in order to drive off any ether 
still remaining, as well as the fatty acids. Carbonate of zinc is now 
added and the solution heated to 100° C. and filtered. The filtrate 
is evaporated on a water-bath until crystallization begins, when it 
is allowed to cool and treated with a few drops of absolute alcohol, 
in order to effect a complete separation of the lactate of zinc. The 
solution is then allowed to stand exposed to the air uutil a constant 
weight is obtained. 

From the blood of living dogs Irisawa was able to obtain lactic 



THE BLOOD. 47 

arid iu every case, and it was, moreover, observed that the amount 
found stood in direct relation to the degree of anaemia produced. 

Biliary Constituents. 

Biliary constituents — i. c, bile-pigment and biliary acids — are not 
encountered in the blood under normal conditions, but are found 
there whenever they are present in the urine (which see). It is note- 
worthy, furthermore, that bilirubin may frequently be demonstrated 
in the blood when a urinary examination in this direction yields 
negative results, and, according to von Jaksch, bilirubin occurs in the 
blood in nearly every case in which urobilin exists in the urine, show- 
ing that bile-pigment circulating in the blood is, in all probability, 
transformed into urobilin in the kidneys. 

A cholcemia is thus encountered in various pathologic conditions 
associated with a resorption of bile from the biliary passages, as in 
obstructive jaundice, an excessive elimination of bile into the intes- 
tinal canal, as well as with au increased destruction of red corpuscles. 

Iu order to test for biliary acids in the blood, the presence of which 
leads to destruction of the red corpuscles, as well as to the circula- 
tory disturbances so constantly encountered, the blood is first treated 
with alcohol, in order to remove the proteids. The biliary acids 
which are present in the filtrate are next transformed into their lead 
salts by means of acetate of lead and ammonia, and thus precipitated. 
After washing with water the precipitate is boiled with alcohol and 
filtered. The lead salts are decomposed by means of sodium carbo- 
nate, the solution again filtered, the filtrate evaporated to dryness, and 
the residue extracted with absolute alcohol. The alcohol is distilled 
off, when the biliary salts of sodium will crystallize out, or remain 
behind as an amorphous mass, which may be tested directly according 
to Pe t ten k offer's method. To this end some of the residue is dissolved 
in water and treated with two-thirds of its volume of concentrated sul- 
phuric acid, care being taken that the temperature does not rise be- 
yond 60° C. To this mixture a few drops of a 20 per cent, solution 
of cane-sugar are added, when in the presence of biliary acids a 
beautiful violet color is obtained, which is referable to the action of 
furfurol, formed from the cane-sugar and the acid, upon the biliary 
acids. 

Bilirubin can be demonstrated in the blood most readily in the 
following manner: 10 to 15 c.c. of blood, obtained by means of 
cupping-glasses, are allowed to coagulate, when the serum is removed 



48 CLINICAL DIAGNOSIS. 

by means of a pipette, filtered through asbestos, and coagulated in as 
thin a layer as possible, at a temperature of 80° C. Under such 
conditions normal serum will present a light straw color, while in the 
presence of biliary coloring-matter a light-greenish color is obtained, 
which becomes grass-green ou standing. Should the serum contain 
haemoglobin, as in cases of haemoglobinaemia, a brownish color results. 

Acetone. 

Acetone has been found in cousiderable amounts in the blood 
under various pathologic conditions, aud especially in fevers. 

In order to demonstrate the presence of acetone in the blood this 
is first extracted with ether and subsequently distilled, when the 
distillate is tested as indicated elsewhere. (See Acetonuria.) 

MICROSCOPIC EXAMINATION OF THE BLOOD. 

The Red Corpuscles. 

Variations in the Size of the Red Corpuscles. If a drop of 
blood, most readily obtained from the tip of a finger or the lobe of 
the ear, be examined with the microscope, a large number of faintly 
yellow, non-u ucleated, circular, bicoucave disks will be observed : 
the red corpuscles, or erythrocytes of the blood (Plate II., Fig. 1). 

Under normal conditions variations in the size of the red corpus- 
cles are observed, and Hayem distinguishes between corpuscles of 
average size, measuring from 7.2 u to 7.8 a in diameter, small corpus- 
cles, presenting an average diameter of from 6 u. to 6.5//, and large 
corpuscles, measuring from 8.5/1 to 9 a. 

In certain diseases which are aecompauied by a marked oligocy- 
themia both abnormally small and large corpuscles are encountered, 
which have been termed microcytes and macrocytes. respectively. 
The former measure from 3.5 a to 6 fi, the latter from 9.5/7. to 12 v. in 
diameter. Still larger forms, the megalocytes. or giant corpuscles of 
Hayem, are also at times seen in which the diameter measures from 
10 [i to 16//.. These latter are of considerable importance, as their 
presence in large numbers appears to be confined almost entirely to 
the blood of pernicious anaemia. In chlorosis they are far less 
common. 

The terms microcythoemia and macrocythcemia have been applied 
to conditions in which the smaller or the larger forms, respectively, 
predominate in the blood. TThile there appears to be no doubt that a 



PLATE I 



FIG. 1. 



FIG. 2. 




Elements of Normal Blood ; showing; Red Corpuscles 

Various Forms of leucocytes and Blood 
Plates. (Unstained specimen.) 



Poikilocytosis. Taken from a case of Perni- 
cious Anaemia. (Unstained specimen.) 




• 



The Various Elements of Blood, stained with Hhrlich's Tri-acid Stain, showing Red Corpuscles, 
Nucleated Red Corpuscles and the Various Forms of Leucocytes. 



FIG. 4 






Blood taken from a case of Splenic Leukaemia, showing the Large Increase in the Number 
of Leucocytes. (Unstained specimen.) 



THE BLOOD. 49 

true macrocythsemia exists in the circulating blood in various forms 
of amemia, and while microcytes also may occur, as such, in the cir- 
culating blood, the latter arc only exceptionally met with, the ordi- 
nary microcythsemic condition, according to Hayem, being artificially 
produced during the preparation of the specimen, so that this term 
really conveys a wrong impression and should be discarded. Ad- 
mitting the correctness of Hayem's view to a certain degree, there 
can be no doubt that, under pathologic conditions, abnormally 
small red corpuscles are quite constantly met with in large numbers, 
be they pre-existent, as such, in the circulating blood, or produced 
artificially during the preparation of the specimen. They are thus 
seen accompanying the condition of macrocythaernia, in pernicious 
anaemia, leukaemia, the pseudo-leukaernic condition of children, the 
various severe anaemias in general, and even in chlorosis. 

Variations in the Form of the Red Corpuscles. Going 
hand in hand with variations in the size of the red corpuscles there 
are variations in form, and both microcytes and macroeytes, particu- 
larly the latter, generally do not present the normal circular appear- 
ance, but abnormalities in form, noted in connection with those of 
normal size (Plate II., Fig. 2). Corpuscles are thus seen which 
resemble a flask, a kidney, a biscuit, an anvil, etc., while others^ 
again, present such irregularities that it is impossible to compare 
them with any known object. 

The term poikilocytosis has been applied to alterations both in the 
size and in the form of the red corpuscles. This condition may be 
observed in the various forms of anaemia, and is especially pronounced 
in pernicious anaemia, of which disease this condition was once 
thought to be pathognomonic. In chlorosis, poikilocytosis is usually 
seen in only the most severe cases, and particularly in those mani- 
festing a tendency toward thrombosis and embolism. 

Variations in the Number of the Red Corpuscles. The 
number of red corpuscles in the blood of healthy individuals is 
fairly constant, and the statement generally found in text-books that 
5,000,000 to 5,500,000 are contained in every cbmm. of blood in 
the adult male and 4,500,000 in the adult female is probably 
correct. 

An increase in the number of red corpuscles is noted almost ex- 
clusively in conditions associated with a loss of large quantities of 
fluid from the blood. It is thus especially encountered in the so- 
called algid state of cholera Asiatica, where from 6,200,000 to 

4 



50 CLINICAL DIAGNOSIS. 

6,500,000 may be found in the cbmm. In the ordinary forms of 
severe diarrhoea an increase of 1,500,000 is also by no means rare. 
"While there can thus be no doubt that a polycythemia does occur, 
experiments have demonstrated almost conclusively that such a con- 
dition does not exist in what is generally spoken of as true plethora, 
and that the various symptoms of plethora, formerly attributed to 
an increase in the total amount of blood or of the red corpuscles, 
are referable, more likely, to vasomotor disturbances. 

A diminution in the number of red corpuscles, on the other hand, 
is frequently observed ; it may be temporary, when following hem- 
orrhages, for example, or permanent. An oligocythemia is thus ob- 
served in various forms of anaemia, of whatever origin, where the 
number may fall to 360,000, and even lower in fatal cases. In per- 
nicious anaemia the lowest figures have been noted, and Quincke cites 
a case in which just before death only 143,000 red corpuscles were 
counted in the cbmm. 

When the anaemia is progressive the body apparently becomes 
habituated to the diminution in the number of red corpuscles, and 
it is surprising to find individuals attending to the duties of every- 
day life with a blood-count of only 2,000,000, or even less. It is 
not uncommon to meet with cases of pernicious anaemia in hospitals 
in which patients with only 500,000 corpuscles are not even obliged 
to go to bed. Nevertheless it must be admitted that, whenever the 
number falls beneath this figure, recovery is probably out of the 
question. A sudden reduction in their number to 1,000,000, more- 
over, is usually followed by a fatal result. 

Nucleated Red Corpuscles. Two varieties of nucleated red 
corpuscles may be seen : 

1. Normoblasts : These are nucleated red corpuscles of the size 
of an ordinary erythrocyte, and appear to be identical with those 
normally found in the bone-marrow of adults. The nucleus of nor- 
moblasts, which frequently shows signs of undergoing division, is 
usually situated centrally, although an excentric position of the same 
is not infrequently observed. These forms are further characterized 
by the great aviditv with which their nuclei take up stains (Plate 
II., Fig. 3). 

Free nuclei, undoubtedly derived from the normoblasts, may also 
be met with as such in the blood. 

2. Megaloblasts, or gigantoblasts of Ehrlich : These elements are 
from three to five times as large as a normal erythrocyte, and are pro- 



THE BLOOD. ;, 1 

videdwith a large nucleus, which, according to Ehrlich, never mani- 
fests signs of undergoing division, however, and is rarely stained as 
deeply as the normoblastic nucleus (Plate II., Fig. 3). As the 
megaloblasts are normally met with only in foetal bone-marrow Ehr- 
lich views their presence in the blood oV adults as a symptom of de- 
generative metamorphosis. Their presence in the blood in the absence 
of normoblasts he furthermore regards as a very grave symptom. 
Recently, however, Askanazy has reported a case of bothriocephalic 
anaemia in which megaloblasts in large numbers, but scarcely any nor- 
moblasts, could be discovered in the blood, and in which the patient 
recovered completely after the expulsion of sixty-seven parasites. 
The same observer also noted that the .nuclei of megaloblasts may 
undergo indirect division, and that the nuclei of normoblasts fre- 
quently present the picture of karyorhexis. He concludes that a 
material difference does not exist between normoblasts and megalo- 
blasts, and that the former develop from the latter. 

Megaloblasts are especially numerous in pernicious anaemia and leu- 
kaemia, while in the so-called secondary anaemias they occur in only 
small numbers and are at the same time much degenerated. As a 
rule, nucleated red corpuscles cannot be made out in fresh prepara- 
tions, and it is generally necessary to stain the blood according to 
special methods (see pp. 60). 

The Leucocytes. 

The leucocytes, or colorless corpuscles of the blood, as seen in 
freshly prepared specimens, are roundish or irregularly shaped cells, 
being mostly larger than the red corpuscles ; they are nucleated, and 
many are distinctly granular in appearance, so much so, in fact,, that 
the nuclei are often entirely hidden from view (Plate II. , Fig. 1). 
In a carefully prepared specimen leucocytes will often be met with 
which are endow r ed with the power of locomotion, creeping over the 
field of the microscope by throwing out pseudopodia in a manner 
analogous to that seen in amoebae. In their general mode of living 
these motile leucocytes, moreover, closely resemble the latter organ- 
isms, and it is most interesting to observe the manner in which 
these little bodies take up cellular debris, and even obnoxious organ- 
isms that may be present in the blood. In malarial blood, for ex- 
ample, in which, as will be shown more particularly later on, certain 
amoebic parasites are present, one is not infrequently able to observe 



52 



CLINICAL DIAGNOSIS. 



leucocytes approach these bodies and take them up by flowing around 
them, as it were (Fig. 12). Metschnikoff even regards this function 
01 the leucocytes as their most important one. Those leucocytes 
which possess this power of removing foreign matter from the blood 
have been termed phagocytes by this observer ; and, according to 
his views, the outcome of a bacterial invasion of the body, figura- 
tively speaking, will depend upon the superiority of the organisms 
engaged in warfare. The term phagocytosis has been applied to the 
destruction of bacteria by leucocytes. 



Fig. 12. 




Phagocytosis. 



Variations in the Number of the Leucocytes. While the 
number of red corpuscles is subject to very slight variations under 
physiologic conditions, that of the leucocytes varies within fairly 
wide limits, being influenced by the age and sex of the individual, 
pregnancy, the process of digestion, the character of the blood- 
vessel from which the specimen is taken, etc. 

According to Osier, the number of leucocytes per cbmm. of blood, 
obtained from the finger or the ear, normally varies between 5000 



THE BLOOD. 53 

and 7000, so that taking 5,000,000 as the average Dumber ol red 

corpuscles per cbnnn., the ratio between the two would vary between 
1:1000 and 1 : 714. 

In women a smaller number of leucocytes is found, according to 
Moleschott, than in men, while Hayem was unable to observe any 
difference. 

An increase in the number of leucocytes, to which condition the 
term leucocytosis has been applied by Virchow, is met with under 
both physiologic and pathologic conditions. As Goldscheider 
rightly suggests, it would be better, however, to restrict the term 
leucocytosis to indicate the number of leucocytes in a general way, 
while an increase in their number should be spoken of as hyperleu- 
cocytosis, and a diminution in their number as hypoleucocytosis. 

Physiologic Hyperleucocytosis. An increase in the number 
of leucocytes occurring in health is noted especially in children, dur- 
ing the process of digestion, in pregnancy, following the use of cold 
baths, etc. 

According to Hayem, about 18,000 leucocytes are found in the 
blood of infants during the first eighty hours of life, 8000 during the 
first month, while in children aged from several months up to the 
fourth year 6000, and in adults and old age only 5000 are counted 
on an average, according to the same observer. 

An idea of the marked increase occurring during the process of 
digestion, constituting the physiologic ' ' digestive leucocytosis " of 
Virchow, may be formed from the accompanying diagram, to which 
two charts have been added, illustrating the diurnal variations in the 
amount of haemoglobin and the number of red corpuscles (Fig. 13). 

This form of hyperleucocytosis appears to be more marked in 
health than in disease, and notably in gastro-intestinal diseases. 
Schneyer was thus able to note the absence of a digestive hyperleu- 
cocytosis in every one of the eighteen cases of carcinoma of the stomach 
observed by him, and records five similar cases described by Muller. 
In almost all cases of ulcer of the stomach and of benign stenoses 
of the pylorus, on the other hand, the usual increase in the number 
of leucocytes could be established. Should further investigations 
confirm the results thus reached, it is apparent that an examination 
of the blood in this direction would be of the greatest importance 
in the differential diagnosis between carcinoma and ulcer of the 
stomach. 

A very marked increase is frequently noted after a cold bath, 



54 



CLINICAL DIAGNOSIS. 



which, according to Thayer, may even amount to 284.6 per cent. 
In his own person on one occasion the leucocytes, which numbered 
3250 per cbmm. before the bath, rose to 12,500 twenty minutes later. 
As the observer reports, however, that he was blue and shivering at 
the eud of his bath, the stimulus given can hardly be regarded as 
having produced only a physiologic effect. 

Fig. 13. 
Red corpuscles in 1 cbmm. of blood. 



[ill. 






8 


A.M. 
10 


I 


2 


P.M. 

4 6 8 


10 


1 


2 i 


A.M. 

4 


3 8 














II 1 1 1 1 


5,4 














M 
















\ ^^\ 




S^/l 1 Kl 








5,2 
5,1 

5,0 














\ 1 / \ 


/ 




"^ 




< 




\ / 
















v 













Hb. in 1 cbmm. of blood. 



0,140 




*-^^ V \ 




/ 


\ 








>>~~~~~~\ / 


N 






130 


^ \ ^-^*"~ 






\ / 


0,12-3 


V^ / 










' 



Leucocytes in 1 cbmm. of blood. 





























8000 




























1 












/ \ 


7500 
















/ 1 \ iiil M-i i i 










/ v . /I I IN. 1 1 1 










7000 




l/l l\ 1 / N 




























/ 






6500 
















\ 










1 / 


V \ 


6000 


^ 


(/ 


\ 










\ / 


5500 










\ / 
















\ / 




wwi 
















* 





Diagram showing the diurnal variations in the number of red corpuscles, the amount 
of heemoglobin, and the number of leucocytes. (Taken from Keixert.) 

The physiologic hyperleucocytosis observed during pregnancy is 
particularly marked during the last live months, and appears to 
occur quite constantly in primiparse, while in multipara exceptions 



THE BLOOD, 55 

are frequently noted. In an analysis of thirty-one cases Etieder 
could thus note the existence of a hyperleucocytosis in twenty, in 
which the Dumber of leucocytes varied betweeu 10,000 and 1G,000, 
with an average of 13,000 per cbrarn. 

Pathologic Hyperleucocytosis. Under pathologic conditions 
an increase in the number of leucocytes is frequently observed and 
ia a matter of great importance. 

.V leukaemia, in which the greatest increase in the number of leu- 
cocytes is noted, may thus be diagnosed at once by an enumeration 
of the leucocytes, a single glance through the microscope often being 
sufficient to determine the diagnosis (Plate II., Fig. 4). This in- 
crease is most pronounced in cases of the lieno-myelogenous form, 
in which the proportion of white to red cells may be 1 : 10, 1 : 5, or 
even 1:1; and Osier states that cases have been recorded in which 
the leucocytes actually outnumbered the red corpuscles. In the 
lymphatic form of leukaemia this increase is not so marked, and the 
proportion of 1 : 10 but rarely exceeded. 

Aside from leukaemia a hyperleucocytosis is observed in all acute 
cases of inflammation, and it may be said that the increase in the 
number of the leucocytes is directly proportionate to the degree of 
the local reaction, so that it is possible to say in a given case whether 
or not a hyperleucocytosis will occur. In typhoid fever, for exam- 
ple, in which the local reaction is slight, no hyperleucocytosis, or 
one of only mild degree, will be observed, while with a compli- 
cating pneumonia or pleurisy, in which the local reaction is well pro- 
nounced^ correspondingly marked hyperleucocytosis will be found. 
This is most important, as complications in this disease may thus 
often be discovered by an examination of the blood, and in con- 
junction with the cliuical symptoms a correct, or, at least, a probable, 
diagnosis may often be reached, which would have been out of the 
question otherwise. 

To cite only one example : A convalescent from typhoid fever sud- 
denly began to complain of pains in the abdomen, particularly marked 
in the right iliac fossa, which increased within a few hours to such a 
degree that full doses of morphine aud chloroform inhalations became 
imperative. Four hours later the patient was comatose, with a pulse 
ranging from 160 to 200 and a temperature of 105.5° F. At this 
stage an examination of the blood showed an approximately normal 
number of leucocytes. Within the next twenty-four hours icterus, 
accompanied by the passage of bile-colored urine aud clay-colored 



56 CLINICAL DIAGNOSIS. 

feces, developed, and the next dav a biliary calculus was found in 
the stool. The diagnosis of cholelithiasis was based upon the result 
of the blood-examination in conjunction with the clinical symptoms. 

An osteomyelitis may be similarly recognized at a time when the 
clinical symptoms in themselves alone would not warrant the diag- 
nosis. 

In pneumonia the degree of hyperleucocytosis may serve as a direct 
index of the amount of lung-tissue involved, disappearing during 
the crisis, or even a few hours before it sets in. 

The hyperleucocytosis here is quite constant, excepting, according 
to Tschistovitch and von Jaksch, certain cases in which it is absent, 
or but slightly marked, and which, according to the same authorities, 
are invariably fatal. The results reached at the Johns Hopkins Hos- 
pital, however, do not appear to bear out the correctness of this view, 
as fatal cases were observed in which 45,000 and even 114,000 leu- 
cocytes were counted per cbmm. Further investigations in this 
direction are urgently needed, and, should the general results obtained 
by Tschistovitch and von Jaksch be confirmed, a blood-examination 
in pneumonia would be of the greatest prognostic value. As in 
pneumonia, so also in erysipelas, the hyperleucocytosis terminates 
by crisis. 

A cachectic hyperleucocytosis, often of great intensity, is noted in 
cases of malignant disease ; but it is still an open question whether 
or not this is dependent upon the local reaction in the neighborhood 
of the growth. To judge from personal observations, the existence 
of a hyperleucocytosis in the differential diagnosis between malig- 
naut and benign diseases of the stomach invariably points to the 
former. 

General Differentiation of the Various Forms of Leuco- 
cytes. Upon ordinary microscopic examination three varieties of 
leucocytes can be distinguished. Some are round, smaller than a 
red corpuscle, and provided with a large, round nucleus, which is 
surrounded by a very narrow rim of non-granular protoplasm. 
Others are met with which are likewise round, of the size of an 
ordinary red corpuscle, the large single nucleus being surrounded 
by a narrow zone of non-granular protoplasm. Finally, the large 
amoebic cells, the bodies of which are filled with granular material, 
often hiding the nucleus from sight, are representatives of the third 
variety. 

Upon further examination differences mav also be demonstrated 



THE BLOOD. 57 

iu the character oi the granulations. Some Leucocytes will thus be 

observed in which these are very line, giving the entire body of the 
cell a cloudy appearance, usually obscuring the nucleus, which may 
be brought into view, however, together with its nucleoli, by treating 
the preparation with a drop or two oi' a 1 per cent, solution of acetic 
acid. On the other hand, very coarse granulations may be observed 
in certain leucocytes, while still others, as already pointed out, are 
apparently nou-granular. 

Within late years Ehrlich has studied these various granulations 
in their behavior toward anilin-dyes, the results obtained being most 
interesting, and, as will be shown, oi* decided value from a clinical 
standpoint. He was able to demonstrate the existence oi' different 
chemical affinities between these minute particles of protoplasm and 
the reagents employed. Some are thus only colored by acid stains, 
others again only by those of a basic nature, while still others are 
stained only by neutral stains. 

The Anilin-stains. Ehrlich divides acid stains derived from 
coal-tar into two large groups: i. e., into stains which will color 
the granulations (see below), even when employed in concentrated 
solutions of glycerin, and into those which can only be employed 
in aqueous solutions. 

The first group contains : 

(1) The highly acid bodies belonging to the fluorescin series, viz., 
eosin, methyl-eosin, coccin, pyrosin J aud R, ; (2) the highly acid 
nitro-bodies, such as aurantia ; (3) the two groups of sulpho-acids — 
i. e., indulin, bengalin, aud uigrosin, on the one hand, and the azo- 
stains tropseolin, Bordeaux, and Ponceau on the other. 

The second group contains : 

(1) Fluorescin and chrysolin ; (2) ammonium picrate and uaph- 
thy lam in-yellow ; (3) orange and true yellow. 

Representatives of the basic stains are : Fuchsin (rosanilin), the 
methyl derivatives of rosanilin, viz., methyl-violet, methyl-green, 
etc., the phenyl derivatives of rosanilin (triphenyl-rosanilin), roso- 
naphthylamin, cyanin, safranin, etc. 

As an example of a neutral stain there may be mentioned the 
picrate of rosanilin. 

Differentiation of the Leucocytes according- to their Beha- 
vior toward Anilin-stains. According to their behavior toward 
these various pigments, Ehrlich has divided the granular leucocytes 
found in the blood into eosinophiles, basophiles, and neutrophiles. 



58 CLIXICAL DIAGXOSIS. 

By the aid of bis methods the following forms of leucocytes, the 
study of which is especially important in the differential diagnosis of 
leukaemia, may be made out in the blood. (Plate II., Fig. 3.) 

1. Small mononuclear leucocytes ; these are mostly smaller than 
the red corpuscles, or of equal size. They are devoid of granular 
matter, each cell being provided with a large, deeply staining nu- 
cleus, surrounded by a narrow rim of non-granular protoplasm. 
As they appear to be formed, to a large extent at least, in the 
lymphatic glands, they are also spoken of as lymphogenic leuco- 
cytes or lymphocytes. 

The increase in the number of leucocytes observed in the lymph- 
atic form of leukaemia occurs in this variety only, while the large 
mononuclear elements, as well as the polynuclear leucocytes, are 
at the same time to a considerable extent relatively diminished in 
number. In the lineo-myelogenic form, on the other hand, the 
lymphocytes are relatively diminished. 

2. Large mononuclear leucocytes : these are larger than the red 
corpuscles, their nuclei oval or elliptical in form, and surrounded 
with a somewhat wider zone of protoplasm, which, as in the first 
variety, is apparently non-granular. The origin of these has not 
as yet been definitely ascertained, but it is generally believed that 
they are formed both in the spleen and in the bone-marrow. 

3. Cells which are of the same size as those belonging to the 
second variety, or a little smaller, and filled with very fine neutro- 
philic granules, the c-granulations of Ehrlich. The nucleus is a long 
body, which is twisted upon itself into irregular forms, often present- 
ing a broken appearance, and conveying the impression as though 
several nuclei were present. Such leucocytes are hence spoken of as 
polynuclear neutrophilic leucocytes. As Ehrlich has suggested, the 
polynuclear appearance, however, is probably referable to post-mor- 
tem changes, the condition of the nuclei being in reality polymor- 
phous. They are formed in all probability both in the spleen and 
in the bone-marrow. While basophilic and eosinophilic granules 
have been found in all animals examined in this direction, it is in- 
teresting to note that neutrophilic granules occur only in man, an 
observation which may be of considerable importance in the medico- 
legal examination of the blood. 1 The ordinary forms of hyperleuco- 
cytosis are referable to an increase in the number of these elements. 

1 This statement, which was made by Lenhartz, has recently been contradicted by Xiegolewski, 
who claims that neutrophilic leucocytes occur in the blood of all vertebrate animals. 



THE BLOOD. 59 

All pus-corpuscles, moreover, according to Ehrlich, belong to this 
class. 

4. Cells are encountered in every specimen of blood which appear 
to be transition-forms between the second and third varieties. These 
are mononuclear, the nuclei, however, presenting a constricted ap- 
pearance, indicating that the cells are beginning to become polymor- 
phous. As a general rule no granulations are found, but exception- 
ally they do occur, when they are neutrophilic in character. 

5. Cells which are of the size of the third variety, provided with 
a single, ovoid, or polymorphous nucleus, and large, ovoid, or round- 
ish, highly refractive, fat-like granulations, the a-granulations of Ehr- 
lich. The latter only take up acid stains, such as eosin, and are 
hence spoken of as eosinophilic leucocytes. According to Ehrlich, 
these leucocytes are derived from the bone-marrow only, and have 
hence also been termed myelogenic leucocytes. There appears to be 
some doubt, however, as to the correctness of this view, as marked 
differences can be shown to exist between the eosinophilic leucocytes 
that are found in the circulating blood and those encountered in the 
bone-marrow. The latter are essentially myelocytes (see below), in 
which eosinophilic granules are found. Their presence in the blood, 
according to recent researches, appears to be confined to leukaemia, 
an observation of the utmost importance. Formerly an increase in 
the number of the ordinary eosinophilic leucocytes was regarded as 
almost pathognomonic of the lieneo-myelogenic form of leukaemia. 
While an increase, both relative and absolute, in their number is 
observed in most cases of this disease, it does not occur invariably, 
and careful examinations have shown, moreover, that a similar in- 
crease may be noted not only in other diseases, notably in true bron- 
chial asthma, but at times even in health. 

6. Basophilic leucocytes are accidentally met with in the blood in 
various conditions, and especially in leukaemia, but are as yet of no 
diagnostic significance. The granulations, the y and o granulations 
of Ehrlich, appear to be the same as those observed in the so-called 
mastzellen, found in connective tissue especially ; the same term has 
hence been applied to this particular variety. 

7. Still another form is fouud in the blood under pathologic con- 
ditions, notably in leukaemia, to which the term myelocytes has been 
applied, as they appear to originate only in the marrow of bone. 
These cells apparently represent an arrest or perverted form of de- 
velopment, being essentially large mononuclear leucocytes, the bodies 



gO CLINICAL DIAGNOSIS. 

of which are filled with neutrophilic granules. At times they ac- 
quire a very large size, exceeding that of all other elements occur- 
ring in the blood, but never become amoeboid. 

The presence of large numbers of this variety, which is rarely seen 
in the blood under normal conditions and particularly when associ- 
ated with an increased number of the ordinary leucocytes, and the 
presence of so-called eosinophilic myelocytes, may be regarded as 
highly suggestive of the lieneo-myelogenic form of leukaemia, while 
they are usually absent in the lymphatic form. 

8. Certain polynuclear leucocytes may also be encountered in the 
blood under pathologic conditions, in which no granulations can be 
demonstrated with Ehrlich's triple stain. Nothing is known of 
their significance. 

The leucocytes normally present in the blood occur in definite pro- 
portions, which are quite constant, as shown in the following table : 

Polynuclear neutrophilic leucocytes . . . 60-75 per cent. 

Lymphocytes 20-30 

Large mononuclear leucocytes and transition-forms 6 

Eosinophilic leucocytes 2-4 " 

Mastzellen, less than 0.0 " 

The Drying- and Staining- of Blood. In order to obtain specimens 
of value, cover-slips of the finest grade, carefully cleansed with abso- 

FIG. 14. 

Ehrlich's cover-glass forceps. 
Fig. 15. 





Liusley's cover-glass forceps. 



lute alcohol or with dilute nitric acid, are indispensable. Care should 
also be taken to handle the cover-glasses with forceps only, as the 
warmth of the fingers in itself is sufficient to affect deleteriously the 



THE BLOOD. 61 

specimen of blood. For this purpose specially constructed for- 
ceps, such as those suggested by Ehrlich, will be found of great 
assistance. (Figs. 14 and 15.) The tip of a finger, or preferably 
the lobe oi the ear, should be cleansed with soap and water, alcohol 
and ether. A small drop of blood is then received upon a cover- 
glass and spread out in such a manner that the layer shall not be 
thicker than the diameter oi' a red corpuscle. To this end it is most 
convenient to cover the drop oi' blood with a second cover-glass, 
pressure being avoided, and to draw the glasses apart in a horizontal 
direction. The same result may also be reached by spreading out 
the blood with the edge of a second cover-slip, a fine caruel's-hair 
brush, or a specially devised mica spatula. This step in the prep- 
aration of dried specimens is the most difficult, and requires a cer- 
tain amount of experience as well as care. 

A number of specimens are thus prepared, and when dried at an 
ordinary temperature will keep almost indefinitely. 

If it is desired to make an early examination, the specimens are 
further fixed by exposure to a temperature of from 110°-115° C. for 
a few minutes. Immersion in absolute alcohol, or a mixture oi 
equal parts of absolute alcohol and ether for the same length of time, 
also answers the purpose. Most convenient is the use of formol, a 
mixture of 40 per cent, formic aldehyde in methyl alcohol and 
water. One part of formol is diluted with nine times its volume oi 
water, and one part of the mixture thus obtained with nine times its 
volume oi alcohol. The immersion oi the specimen in the latter 
solution for but one minute will furnish admirable results. The 
continued exposure of the blood to a temperature of from 100°-120° 
C. for from one to two hours can thus usually be dispensed with, 
although it may be advantageously employed in special cases. For 
the purpose of fixing specimens by heat the use of a small coal-oil 
stove, upon which a copper plate measuring 40 x 10 cm. is placed, 
will be found most convenient. Upon the plate the line corre- 
sponding to the desired temperature is ascertained by means of a 
series of drops of water extending from the middle toward either 
end, and noting the line at which bubbles will appear in the water. 
The specimens are then placed just inside of this line. When once 
properly regulated the apparatus, which may very advantageously 
be placed in a box so as to guard against currents of air, will be 
found to furnish a fairly constant temperature. A drying-oven 
may, of course, be used for the same purpose. 



Q2 CLINICAL DIAGNOSIS. 

When fixed according to one of the methods indicated, the dried 
specimen is ready to be stained. For this purpose a number of 
solutions may be employed, the selection of the special mixture de- 
pending upon the particular points to be elicited. 

Staining with Eosin. A 0.1-0.5 per cent, aqueous solution 
or a 0.25-0.5 per cent, alcoholic solution is used, upon which the 
dried specimen is allowed to float from ten to twenty minutes 
if the former is used, while one-half or one minute only is necessary 
in the case of the latter. It is then rinsed with water, dried between 
layers of filter-paper, and mounted in xylol-balsam. 

The red corpuscles are stained a bright red, the protoplasm 
of the leucocytes a faint red, while the eosinophilic granules are 
deeply colored. 

Staining with Ehrlich's Tri-glyceein Mixture. This is 
composed of 2 grammes each of eosin, aurantia, and nigrosin in 30 
grammes of glycerin. The specimens are allowed to remain upon 
the stain from sixteen to twenty-four hours, when they are rinsed 
in water, dried, and mounted as described. 

The red corpuscles are colored orange, the bodies of the leucocytes 
a dirty gray with dark nuclei, and the eosinophilic granules a bright 
red. 

Staining with Ehrlich's H^matoxylin-eosin. The solu- 
tion is prepared by dissolving 4-5 grammes of hematoxylin in a 
mixture of 100 grammes each of distilled water, alcohol, and gly- 
cerin. To this solution 20 grammes of glacial acetic acid and 
an excess of alum are added. After exposure to the sun for four 
to six weeks about 1 per cent, of eosin is finally added. The speci- 
men is left in the stain exposed to the sun in a covered beaker for 
twenty-four hours, when it is rinsed in water, dried, and mounted. 

The red corpuscles are colored a bright red, the nuclei of the 
normoblasts and megaloblasts a deep black, the bodies of the leuco- 
cytes a light lilac, their nuclei a dark lilac, the eosinophilic granules 
a bright red, while the bodies of the lymphocytes are scarcely stained 
at all and their nuclei appear only a shade lighter than those of the 
nucleated red corpuscles. 

Staining with Ehrlich's Tri-acid Stain. This is the differ- 
ential stain mostly used at the Johns Hopkins Hospital, and one 
which usually furnishes excellent results. It has the advantage also 
that an exposure of the specimen to the stain for six to eight min- 
utes only is necessary. Its preparation requires some care, and it is 



THE BLOOD. 



(>:j 



important, furthermore, thai the mixture should stand for one to 
two weeks before being used. Saturated aqueous solutions of acid 
fuchsin, orange (i, and methyl-green are first prepared and allowed 
to stand until clear, when they are gradually mixed in the propor- 
tions indicated below. 



Fuchsin solution 
Distilled water 

Orange solution 
Methyl-green solution 
Alcohol (94 per cent.) 
Distilled water 
Glycerin 



9 c.c. 

6 " 

is •• 

20 " 

15 " 

30 " 

5 " 



After staining from six to eight minutes the specimen is rinsed 
in water, dried, and mounted. 

The nuclei of the leucocytes are stained a greenish-blue, those of 
the red corpuscles nearly black, the red corpuscles yellow, the eosino- 
philic granules red, and the neutrophilic granules a violet or a lilac 
color. (Plate II. , Fig. 3.) 

Staining with Aronsohn and Philips's Modified Tri-acid 
Stain. Saturated aqueous solutions of orange G, acid rubin, and 
methyl-green are prepared as described above, when the various in- 
gredients are mixed in the following proportions : 

Orange solution 55 c.c. 

Acid rubin solution 50 " 

Distilled water 100 " 

Alcohol 50 " 

To this mixture the methyl-green solution is added, 65 c.c. 



Distilled water 
Alcohol . 



50 
12 



The mixture should stand from one to two weeks before being 
used. 

A drop of the solutiou added to a Petri-dishful of water is em- 
ployed for staining-purposes, an exposure of the specimen for twenty- 
four hours being required. The specimen is then rinsed off in water, 
absolute alcohol, cleared in origanum oil, and mounted. 

The various elements of the blood are colored as with Ehrlich's 
stain. 

Staining with Chenzinsky-Plehn's Mixture. This con- 
sists of 40 grammes of a concentrated alcoholic solution of methylene- 



54 CLINICAL DIAGNOSIS. 

bin - a "nes >i a 0.5 per oent solution ol eosiu in 70 per cent. 

alcohol, and 40 grammes of distilled water. The specimen is stained 
I ■--. or hours. 

The red corpuscles assume the color of eosin, while the eosinophilic 
grannies are bright red and the nuclei of the leucocytes blue. 

Staining with Ehrlich's Nedtrax Mixture. This consists 

five volumes oi a saturated aqueous solution oi acid fuchsin. to 

which one volume of a concentrated aqueous solution oi inethylene- 

blue is added slowly, while shaking. This mixture is treated with 

five volumes oi distilled water and filtered after havin_ s: :: '. : ; 

rral days. The spec:---::- :. s::vl-e; ::::c ~ : 

minutes. 

The red corpuscles present the color of the iuchsin. their nuclei 
as well as those of the leucocytes are black or a light lilac, the 

sinophilic granules red. and the neutrophilia granules violet. 

Spbciax Staining of Basophilic Leucocytes. The staining:- 
fluid consists oi 100 c.c. of distilled water, to which 50 c. c. of a 
saturated alcoholic (absolute solution of dahlia are added. Upon 
clearing. 10-12.5 cc. oi glacial a id are added. The speci- 

men is stained from five to ten minutes. A saturated aqueous 
solution of methylene-blue may be employed for the same purpose 
and in the same manner. 

With the exception of bacteria, only the basophilic leucocytes are 
led red), while pus- :■ •:■ r puscles a re b u t f ai ntly tinged. 

A differential enumeration of the various forms of leucocvtes can 

only be carried out in stained - Ehrlich's tri-acid stain 

being the most useful for this pu From 1000-1200 leuco- 

- at least should be counted in order to obtain reliable results. 

The use >i Zeiss's net-micrometer will be found of great value. 

As will g tL. the actual number of leucocytes 

contained in one cbmm. of blood may be readilv ascertained in an 
indirect manner by counting the number of leucocytes and red cor- 
pusci- s - s] tens see 

The Plaques 

In addition to the lei: - and erytl s large numbers of 

small roundie [its are encountered in the blood which are free 

from coloring-matter and may be frequently observed collected into 

small he. - sier puts it, bunches f grapes. Plate II. . 

1 . Th« blood-plates or plaques of Bizzozero. Accord- 



THE BLOOD. 



65 



ing to Hayem, they represent ordinary red corpuscles in an early 
Btage of development, and have hence been termed hsematoblasts by 
him, an opinion, however, which is not shared by many hsema- 
tologists. 

According to Osier, they number, under normal conditions, from 
200,000 to 500,000 per cbmm., and are said by Hayem to occur in 
greatly diminished numbers in the blood in pernicious anaemia, an 
observation, however, which lacks confirmation. In order to demon- 
strate their presence the drop of blood should at once be mixed with 
Hayem's fluid (see p. 66). 



The Enumeration of the Corpuscles of the Blood by the 
Method of Thoma-Zeiss. 

Of the various instruments employed for the enumeration oi* 
blood-corpuscles that of Thoma-Zeiss appears to be the most satis- 
factory. (Fig. 16.) 

Fig. 16. 




Thoma-Zeiss blood-counting apparatus. 

This consists of a capillary pipette (S) having a bulb in its 
upper third, the lower end being graduated in parts numbered 
from 0.1 to 1, while above the bulb a mark bearing the number 
101 is placed. With this goes a counting-chamber (B) measuring 
exactly 0.1 mm. in depth, the floor of which is ruled into sets of 16 
small squares, each small square underlying a space of T -fc^ cbmm. 

Enumeration of the Red Corpuscles. In order to count the 
red corpuscles in a given case with this instrument the tip of a 
finger, or, better still, the lobe of the ear, is punctured with a 
sharp-pointed scalpel, after having been carefully cleansed with 



qq CLINICAL DIAGNOSIS. 

soap and water, alcohol, and finally with ether. The exuding blood 
is drawn into the capillary tube to a given mark, generally to 1 or 
0.5. according to the degree of dilution desired, care being taken 
that no pressure is exerted upon the ringer and that the tip of the 
instrument comes in contact with the blood only. The point of the 
tube is then rapidly and carefully wiped, and the blood diluted, as 
a rule, with a 3 per cent, solution of common salt, which is drawn 
into the pipette until the 101 mark is reached. 

Toison's fluid is still more convenient as a diluent, as the leuco- 
cytes are stained by the methyl-violet, and thus rendered more 
easily visible. It- composition is as follows : 

Distilled water 160 parts. 

Glycerine 30 " 

Sodium sulphate 8 " 

Sodium chloride 1 part. 

Methyl-violet ........ 0.025 " 

Other solutions, such as a 15—20 per cent, solution of magnesium 
sulphate, a 5 per cent, solution of sodium sulphate, Hayem's or 
Pacini's fluid, may also be employed for the same purpose. 

Formula of Hayem's fluid : 

Bichloride of mercury 0.5 grm. 

Sodium sulphate ' grins. 

Sodium chloride 2.0 

Distilled w 200.0 

Formula of Pacini's fluid : 

Bichloride of mercury 2.0 ^rrns. 

Sodium chloride 4.0 " 

Glycerine 26.0 

Distilled water 226.0 

The contents of the bulb are now thoroughly mixed by shaking, in 
which the glass bead E contained in the bulb aids very materially. 
The contents of the capillary tube are then cautiously expelled, as 
the latter practically contains only the di luting-fluid ; a drop of 
the mixture is placed in the counting-chamber, and the cover-slip 
I air being carefully excluded. When properly 
prepare ; . Newl 1 rings should be seen at the margin of 

the drop. After allowing the corpuscles to settle— from three to 
five minute- are generally sufficient — they are counted. At least 



THE BLOOD. 



67 



one whole field, or, if special accuracy he required, two whole fields, 
should he gone over ; i.e., 200 or 100 small squares, respectively, 
when counting the red, and at least four whole fields when counting 
the white. 

It is convenient to count the red corpuscles in sets of four small 
squares, lying side by side in a horizontal direction, note being 
taken of every corpuscle that touches the boundary lines of the large 
squares, no matter whether the body of the cell lies inside or out- 
side of these lines. It will be noted that every large square is sepa- 
rated from its neighbor, both horizontally and vertically, by a row 
of small squares traversed by a mesially placed line, which serves 
as a guide to the next large square. (Fig. 17.) As a general rule, 
it will be found most convenient to ignore these intermediary 
squares, account being taken only of the large ones. 











Fig 


. 17 










f.v 


i 




•* * 


;•; 




•V 


: : 


O 


*.v 










O 2 o 




J o ' 








**Z 






,% u 


o S ■ 


- / 


,°« " 






o°° 


'.V 


■ 


• 




°o°o 


" »°o 


o°»°» 


\ 


« 


!•".* 




■ 


■« 


;°o : 


° °o 


° 


° o ° 


• 


.' 


«*\ 


* 


; 


.V, 


%'" 


:• 


y°o 


;- 


a' 


° » 


■>" o 


°j 


- ; : 


3 


•> o o 


f°" 


v; 


\ 


• 


♦.*. 


', '■> 


»< 


: t 


, oo 


»,v 


o«° 




0° 


,« 


5 o' 




"« 


\= 




;«," 




•«v 


. c 


• 




Yi 


• 


f« 


°o°» 


.;.• 


il. 


— 


'. 


a 3 


°o°o 



Appearance of blood in the Thoma-Zeiss cell. 



In order to calculate the number of red corpuscles contained in 
one cbmm. of blood the total number noted is divided by the 
number of small squares counted, the result giving the average 
number contained in one small square — i. e., in 4 q QQ cbmm. One 
cbmm. of the diluted blood will then contain 4000 times this num- 
ber, and one cbmm. of undiluted blood the product of this figure 
and the degree of the dilution. 

Example : Supposing that 1200 red corpuscles were counted in 400 
small squares, the average number contained in one — i. e., in ^g-g- 
cbmm. of diluted blood — would be 3, corresponding to 12,000 corpus- 
cles for each cbmm. ; supposing, further, that the blood was diluted 200 
times, we should find 2,400,000 in one cbmm. of the undiluted blood. 

Enumeration of the "White Corpuscles. With this instrument 
the leucocytes, when present in increased numbers, may also be 



6g CLINICAL DIAGNOSIS. 

counted, at least four whole fields, as indicated above, being taken 
into account. 

With an approximately normal number of leucocytes it is necessary 
to resort to special pipettes, which are constructed so as to permit 
of obtaining a mixture of 1 : 10 or 1 : 20. With the diluting-fluids 
mentioned above it would be impossible to count the leucocytes 
in a mixture of this proportion, as a large number would be con- 
cealed by the red corpuscles. An 0.3-0.5 per cent, solution of acetic 
acid is therefore used, which destroys the red corpuscles and renders 
the nuclei of the white more distinct. In the absence of a special 
instrument, an ordinary 1 cbmm. pipette accurately graduated in 
tenths may be employed. 0.9 c.c. of the acetic acid solution is 
placed in a watch-crystal and there mixed with 0.1 c.c. of blood, 
when the counting-chamber is filled and covered as described. In 
order to obtain greater accuracy the entire field of the microscope 
is now counted, a lower power being employed with which the rul- 
ings are just visible. The cubic contents of the field are now deter- 
mined according to the formula Q = ;rr 2 X 0.1. Q represents the 
cubic contents to be determined ; r, the radius, which is readily 
ascertained by noting the number of vertical lines which cross the 
field, bearing in mind that the distance between two of these is equiva- 
lent to ■£$■ mm. (the area of each small square being T l ¥ mm.), and 
dividing the transverse distance by 2 ; the value, tc. is constant, 
3.1416 ; 0.1 represents the depth of the chamber. 

If n represents the number of white corpuscles contained in the 
field, the cubic contents of which are Q, the number of corpuscles, 
N, contained in one cbmm. of the diluted blood is ascertained ac- 
cording to the equation : 

Q : n : : 1 : N and N = -. 
Q 

As the blood has been diluted ten times, the value of N for the 

non-diluted blood will be ~, where n represents the total number 
of leucocytes and f the number of fields counted. 

Example : Supposing the number of leucocytes found in 50 fields 
to have been 600, and the cubic contents of each field 0.03925 cbmm. , 
the total number of leucocytes contained in one cbmm. of undiluted 
blood, according to the equation ; 

N== 10.n 10:600 



f.Q 50:0.03925 
would be 3057. 



THE B LOO D. 69 

Special care should be taken to keep the pipette in clean condition. 
After use it should be rinsed with (1) the diluting-fluid, (2) dis- 
tilled water, (3) absolute alcohol, and (4) ether. If dust or coagu- 
lated blood adhere to the pipette, it should be removed by repeated 
rinsings with strong acids or alkalies, assisted if necessary by a 
bristle. 

Indirect Enumeration of the Leucocytes. 

The number of leucocytes may also be ascertained in an indirect 
manner by accurately counting the number of red corpuscles and 
leucocytes in dried and stained specimens with a Zeiss net-microm- 
eter, the ratio between the two varieties being thus ascertained. 
With the Thoma-Zeiss apparatus the number of red corpuscles con- 
tained in one cbmm. of blood is then determined, when the corre- 
sponding number of leucocytes is found according to the equation : 

1 : r : : L : E, and L = — = 7142, 
r 

where 1 and r represent the number of leucocytes and erythro- 
cytes, respectively, counted in the dried specimens, and where L 
indicates the unknown number of leucocytes and R the number of 
red corpuscles contained in one cbmm. of blood, as determined with 
the Thoma-Zeiss instrument. 

Example : Supposing that 700 red corpuscles and only one leuco- 
cyte were counted in the dried specimen, and that an estimation of 
the erythrocytes with the Zeiss apparatus indicated the presence of 
5,000,000 in one cbmm. of blood, the corresponding number of 
leucocytes would be 7142, as is apparent from the* ! calculation : 

L== J5 = 1.5000000 _ 714g 

r 700 

Notwithstanding the apparent simplicity of the process of blood- 
counting, considerable experience is required in the technique in 
order to obtain results that are free from error. In using the 
Thoma-Zeiss apparatus errors of more than 2-3 per cent, should 
not occur. 

The Haematokrit. 

Within late years the centrifugal machine has also been applied 
to blood-counting, and it may be safely asserted that should the 
claims set forth for the hsematokrit, as the instrument is termed, be 



70 



CLINICAL DIAGNOSIS. 



borne out by actual experience, the use of cytometers, which is both 
tedious and fatiguing, will soon be abandoned. 



Fig. 18. 




Fig. 19. 




Daland's latest modification of this instrument, originally devised 
by Hedin, is represented in the accompanying illustrations (Figs. 18, 
19, 20, 21, and 22), and can be strongly recommended to both hos- 



THE HL001). 



71 



>ital physicians and those engaged in general practice. It consist 8 

essentially ol a metallic frame (Fig. 19), supported upon a spindle 
which can be rotated at high speed, one single revolution of the 
large handle causing 134 revolutions of the frame. Two glass 
tubes 50 mm. in length and having a diameter of 0.5 mm., used 
to receive the blood, accompany the instrument. Each tube (Fig. 

Fig. 20. 




Fig. 21. 




21) bears a scale ranging i'rom to 100, the individual divisions of 
which are rendered easily visible by a lens-front. The outer ends 
of the tube fit into small, cup-like depressions, the bottoms of which 
are covered with thin rubber, the inner extremities being held in 



-■2 CLINICAL DIAGNOSIS. 

position by springs. The instrument should be firmly secured to a 
solid table and oiled daily when in use. 

To examine the blood, a rubber tube, provided with a mouth- 
piece (Fig. 22), is slipped over the end of one of the glass tubes, when 
the latter is filled completely by suction from a drop of blood ob- 
tained from the finger or the ear. The blunt point of the tube is 




Daland's h^matokrit. 

then quickly covered with the finger and the tube inserted into the 
frame. This is rotated at a speed of 10,000 revolutions for two or 
three minutes, when the volume of red corpuscles is directly read off. 
In healthy individuals the volume of red corpuscles is about 50 per 
cent., so that in a given case a proportionate expression of the per- 
centage of corpuscles, as compared with the normal, can be obtained 
by multiplying the figure upon the scale by two. 

As it has been ascertained that 1 per cent, by volume represents 
about 100,000 red corpuscles, it is only necessary to add five ciphers 
to the percentage-volume found in order to obtain the number of 
red corpuscles in one cbmm. of blood. 

Example : Supposing that in a given case the reading was 35 ; 
by multiplying this figure by 100,000, 3,500,000 would represent 
the number of red corpuscles contained iu one cbmm. of blood. 

The amount of haemoglobin contained in each corpuscle is ascer- 
tained approximately by dividing the amount of haemoglobin deter- 
mined by means of Fleischl's instrument by the number of corpuscles 
found with the hrematokrit. 

If normal blood be examined with the hsematokrit, the leucoc- 
ytes will be seen to form a narrow white band at the central end 
of the column of red corpuscles. If a leucocytosis be present, it is 
readily recognized even though slight. 

Bacteriology and Parasitology of the Blood. 

It is generally admitted that micro-organisms do not normallv 
occur in the blood ; in conditions which may be said to stand 



THE BLOOD. 73 

midway between health and disease they arc at times met with. 
In patients, for example, suffering from furuncles, bacteria may 

be found in the skin, in the lymphatic glands, and even in the 
blood of neighboring tissues, other symptoms of disease being 
absent, a condition to which the term "latent microbism" has 
been applied by Verneuil. 

Under truly pathologic conditions, on the other hand, micro- 
organisms are not infrequently met with in the blood, and an 
examination with this view will often lead to a correct diagnosis. 
Frequently patients are seen in whom the diagnosis of typhoid 
fever appears most probable, but in whom an examination of the 
blood shows the presence of malarial organisms. It can be truth- 
fully said that, in our latitudes at least, the physician who does not 
resort to the microscope in fever cases ignores an infallible aid to 
diagnosis. 

For ease of reference the various organisms that are met with in 
the blood in disease will be described under the headings of the 
respective diseases in which they are found. 

Acute Miliary Tuberculosis. 

In acute miliary tuberculosis tubercle-bacilli have repeatedly been 
observed iu the blood, but while their presence may be regarded as 
pathognomonic of the disease, the search for them is most tedious 
and often in vain. Nevertheless a careful examination of the blood 
is indicated in doubtful cases, and the fact should ever be borne in 
mind that only a positive result is of value. 

For methods of staining aud a description of the tubercle-bacillus 
the reader is referred to the chapter on Sputum. 

Glanders. 

In glanders the specific bacillus is constantly present in the 
blood, and may be demonstrated by staining the dried prepara- 
tions on a cover-glass for five minutes with a concentrated alco- 
holic solutiou of methylene-blue, mixed just before using with its 
own volume of a 1 : 10,000 solution of potassium hydrate. From 
this mixture the specimen is passed for a second or two into a 1 per 
cent, solution of acetic acid, which has been tinged a faint yellow by 
the addition of a little tropa?olin 00 solution; it is then decolorized 



74 



CLINICAL DIAGNOSIS. 



by washing in water containing two drops of concentrated sulphuric 
acid and one drop of a 5 per cent, solution of oxalic acid for every 
10 c.c. 



Fig. 23. 

/ 



Bacillus of glanders. (Abbott.) 

In specimens thus stained the bacilli appear as short rods, measur- 
ing 2 a to Su in length by 0.3// to 0.4 a in breadth, often contain- 
ing a spore at one end. (Fig. 23.) 

Typhoid Fever. 

In typhoid fever Eberth's bacillus may at times, though rarely, 
be demonstrated in the blood, particularly, it is claimed, when taken 
from the roseolar spots. As an aid to diagnosis, however, no reliance 
should be placed upon the results of such an examination. 

Influenza. 

Iu influenza a specific organism has been described by Pfeiffer 
and Kitasato as occurring in the sputum ; it is also constantly 
present in the blood of such patients. The organism in question 
appears in the form of minute rods measuring 0.1 a in breadth 
by 0.5/7. in length, occurring either singly or in chains of threes 
or fours. In suitably prepared specimens, owing to the fact that 
their poles take up the stain more readily than the middle portion, 
they convey the impression of diplococci. 

Canon advises the following method for demonstrating their pres- 
ence in the blood : Cover-glass preparations that have been allowed 
to dry at an ordinary temperature are placed in absolute alcohol for 
five minutes and then stained at a temperature of 37° C. from three 
to six hours with the Chenzinsky-Plehn solution (see p. 62). The 
specimens are then washed in water, dried between layers of filter- 
paper, and mounted in balsam. Stained in this manner the red cor- 



PLATE HI. 





FIG. 


1. 






if* . 


T 






/ / J 




.. ::k 


/ 


./) 


,. •<, 






rt 


5 : 


i 


.»**""*" 


...•;.'.• 


Streptococcus Pyogenes. 


(Abbott.) 




FIG. 


3. 






A 



FIG. 2. 



°°§^ j 




*%8 



Spirilla of Relapsing Fever, (v. Jaksch.) 






Bacillus Anthracis, highly magnified to 
show Swellings and Concavities at Extremi- 
ties of the Single Cells. 



FIG 4. 






Malarial Parasites: Non-pigmented Intracellular Form. This specimen was taken from a case of 

Pernicious Malaria. The amceboid movements, which the parasite underwent during 

observation, are very well represented. (Unstained specimen.) 



FIG. 5. 



Malarial Parasites: Non-pigmented Intracellular Form, presenting a Shaded Aspect in its Interioi 
Taken from the same patient. (Unstained specimen.) 



FIG. 6. 



Malarial Parasites: Small, Pigmented Intracellular Form. The destruction of the red corpuscle is just 

beginning, as shown by the small number of melanin granules in the interior of 

the parasite. Taken from the same patient. (Unstained specimen ) 



THE BLOOD. 75 

puscles are colored red, and the leucocytes, as well as the bacilli, 

blue. As a rule, only from four to twenty of these are found 
in one preparation, usually occurring singly, but also in groups. 
Owing to the fact that they are found in the blood only during 
the acme of the disease, Canon recommends the examination of the 
sputum for diagnostic purposes, a view with which personal observa- 
tion is entirely in accord. 

Sepsis. 

In septic conditions various micro-organisms are observed in the 
blood, both during life and after death. Pneumococci were thus 
met with in peritonitis, associated with carcinoma of the uterus, in 
cases of suppurative oophoritis, following childbirth, and in cases 
of biliary abscess at the time of a chill. Friedlander's bacillus was 
also found in the latter disease. The staphylococcus aureus has 
been seen in the blood in acute osteomyelitis, .and streptococci 
(Plate III., Fig. 1) have been detected in scarlatinal sepsis, and 
also found associated with local abscesses four days before death. 

In this connection it may be stated that a microscopic examination 
of the blood alone is often not sufficient to detect the presence of 
these organisms, and cultures and animal experiments should be made 
in doubtful cases. To this end the blood should be obtained under 
antiseptic precautions directly from a vein by means of an ordi- 
nary hypodermic syringe, 2 to 3 c.c. being sufficient for all pur- 
poses. 

The utility of an examination of the blood in suitable cases is 
decided ; iu many cases of severe phlegmonous abscesses a direct 
indication for amputation can be obtained in this manner at a com- 
paratively early date. 

Streptococci are frequently met with in the blood of patients dead 
of diphtheria, while the staphylococcus aureus and Loffler's bacillus 
are more rarely seen. In scarlatina and pulmonic phthisis strepto- 
cocci have likewise been observed. 

Relapsing' Fever. 

Relapsing fever is characterized by the presence in the blood, and 
here only, of spirilla or spirochretaB which bear the name of their 
discoverer, Obermeier. In order to search for these organisms no 
special precautions are necessary. After having carefully cleansed the 



76 CLINICAL DIAGNOSIS. 

finger as described, a drop of blood is mounted upon a very thin 
cover-glass, and this directly inverred upon the slide, when the 
specimen is ready for examination ; an oil-immersion lens is not 
required. Attention is drawn to the presence of these organisms 
by certain disturbances noticeable among the red corpuscles, and 
upon careful examination it will be seen that these are caused by the 
wriggling movements of the spirilla. The spirochetal Obermeieri 
are long, slender filaments, measuring from 36 (J. to 40 // in length by 
0.3// to 0.5// in breadth, and present from eight to twelve incurva- 
tions of equal size with tapering extremities. (Plate III., Fig. 2.) 
These last two characteristics serve to distinguish this species from 
that described by Ehrenberg, in which the radius of the incurvations 
is not the same in all, and in which the extremities do not taper. 

The number of spirilla that may be found in a drop of blood 
varies, being greater during the access of the fever, when twenty, 
or even more, may be observed in the field of the microscope. They 
occur either singly or in bunches of from four to twenty, specimens 
such as those figured in the table being frequently seen. In 
the quiescent stage they are sometimes arranged in the form of 
rings or of the figure 8. After the crisis they seem to disappear en- 
tirely from the blood, and their presence during an afebrile period 
may therefore always be regarded as indicating a pseudocrisis. 
During the afebrile periods small, bright, round bodies have been 
described as occurring in the blood, which according to some 
are spores, but according to others merely represent debris of the 
spirilla. 

Culture-experiments have not been very satisfactory, although 
Koch, at a temperature of from 10° to 11° C, observed an increase 
in their number. 

That confusion should ever arise in distinguishing the spirilla 
of relapsing fever from the free flagella observed at times in malarial 
fever would appear very improbable. 

Anthrax. 

The bacillus of anthrax, as first pointed out by Pollender, Brouell, 
and Davaine, is frequently met with in the blood, where it should 
be sought for in doubtful cases by staining according to Loffler's 
method. To this end cover-glass preparations are floated for five 
to ten minutes upon a mixture of 30 c.c. of a concentrated alco- 
holic solution of methylene-blue and 100 c.c. of a 1:10,000 



I THE BLOOD. 77 

solution of potassium hydrate ; they are then washed for five to 
ten seconds in a 0.5 percent, solution of acetic acid, treated with 
alcohol, dried, and mounted in balsam. Thus stained, the bacilli 
appear as rods measuring From 5 a to 12/i in length by 1 /' in breadth, 
usually presenting a segmented appearance, the extremities being 
slightly thickened. Spores are not found, as the organism multiplies 
by fission. When present in large numbers it is not even necessary 
to stain, as the organisms can then be seen without difficulty in fresh 
specimeus. (Plate III., Fig. 3.) 

In doubtful cases in which a microscopic examination of the blood 
yields negative results, a few c.c. of the blood may be injected into 
a mouse or a guinea-pig, in the blood of which the bacilli will 
soon be found in enormous numbers if the disease be anthrax. 

Malaria. 

The discovery of the existence of a definite micro-organism be- 
longing to the class of protozoa, the plasmodium malarias of Laveran, 
in the blood of malarial patients, and of its invariable presence in 
the different forms of this disease, must be regarded as one of the 
most important in clinical medicine. This is not the place to point 
out how frequently a diagnosis of malarial fever based upon clinical 
symptoms alone has proved false, how often a tuberculous, a 
syphilitic, or a septic infection has been overlooked, and termed 
malaria ! It will suffice to say that errors of this kind, in view 
of our present knowledge and the ease with which they can be 
avoided by every physician, should no longer occur. The diagnosis 
of malaria should in every case be based upon a microscopic exami- 
nation of the blood. 

The search for these bodies, it is true, may be very tedious at 
times, but it will always be crowned with success if the disease 
in question be malarial. Again and again the author has seen cases 
in which the clinical symptoms alone would not have warranted the 
diagnosis of malaria, and in which the true nature of the disease was 
cleared up only by a careful examination of the blood; and cases have 
often been seen in which the diagnosis of malaria based upon clini- 
cal symptoms alone was disproved by the absence of plasmodia from 
the blood and by the result of the post-mortem examination. 

While it is true that the life-history cf the organism is as yet only 
imperfectly understood, it being still an open question whether or 



78 CLINICAL DIAGNOSIS. 

not the various forms observed represent different stages in the 
development of one and the same species, this is of no importance 
from a clinical standpoint, and the demonstration in the blood of 
anv one of the forms to be presently described will always warrant 
the diagnosis of malaria. 

The parasite in question, as stated above, is a protozoon and be- 
longs to the class of haBinatozoa, representatives of which are found 
in the blood of various animals, such as the rat, frog, tortoise, carp, 
various birds, etc. 

The following forms are found in the blood of man : 

Small hyaline bodies (Plate III., Fig. 4) enclosed within the red 
corpuscles, the so-called intracelluar non-pigmented form, which may 
be seen to undergo most active amceboid movements. The rapidity 
with which changes in the form of the organism occur is most aston- 
ishing, and sketches of any one phase can often indeed be made only 
from memory. Some experience is necessary to demonstrate their 
presence in the blood, where similar post-mortem appearances, refer- 
able to vacuolation, are normally encountered in the red corpuscles, 
but in which amoeboid movements will, of course, not be seen. 
If any doubt be felt, dry cover-glass preparations should be pre- 
pared and stained, after fixing with alcohol, forinol, or by exposure 
to a temperature of 110° C. for an hour, as described above, with 
Chenzinsky-Plekn's solution, when the red corpuscles will be colored 
a light red, the leucocytes blue, the eosinophilic granules a deep red, 
and the parasites blue. 

A simpler method by which the non-pigmented intracellular form 
may be distinguished from appearances referable to vacuolation is 
the following : 

A drop of a concentrated solution of methylene-blue in 0. 6 per cent, 
salt-solution is placed upon the finger, and a drop of blood allowed 
to flow directly into this, when it is mounted in the usual manner, 
care being taken that as small a drop as possible, both of the stain- 
ing-fluid and of the blood, be employed. The organisms are tinged 
a light blue, while the red corpuscles present their normal color. 
Should any of the latter also be stained, as happens at times, the 
color will be uniform throughout, so that no confusion can possibly 
arise between these and the plasmodia. 

Ordinarily, the staining of blood-specimens for examination is 
unnecessary, fresh specimens being employed, prepared in such a 
manner as to iusure the spreading out of the red corpuscles in 



THE BLOOD. 79 

as thin a layer as possible, all pressure upon the preparation being 
carefully avoided. An oil-immersion lens is here almost a gwie 
qua non. 

While the armvboid movements of the non-pigmented intracellular 
form are usually marked, forms are at times noticed in which they 
are less evident, and in which deviations from a circular form can 
only be observed with difficulty, the organisms under such condi- 
tions presenting a shaded aspect at some point in their interior, 
closely resembling the darker portion in the centre of a normal red 
corpuscle. (Plate III., Fig. 5.) 

According to the author's experience, the non-pigmented intra- 
cellular bodies are usually overlooked in fresh specimens, in which the 
attention of the observer is largely occupied by the pigmented intra- 
cellular forms presently to be described, but in stained specimens 
their presence is unmistakable. In a case of pernicious mala- 
rial fever of the algid type, in which a history of only one week's 
illness without chills was obtained, these non-pigmented intracellular 
forms occurred in such numbers that normal red corpuscles were 
only exceptionally seen. In the same patient small intracellular 
forms in which a few tiny granules of melanin could be distinguished 
were observed ; they occurred in much smaller numbers and disap- 
peared before death. They differ from the large pigmented forms 
(Plate III., Fig. 6) in being more or less circular, and, while pre- 
senting evidence of amoeboid movements, manifested a very distinct 
tendency to return to a circular shape. This particular form was not 
found in the other cases examined by the author at the Johns Hop- 
kins Hospital. It is interesting to note that while numerous ex- 
aminations were made of the blood of this patient during life, no 
other forms were seen, excepting occasionally a few non-pigmented 
extracellular forms. Five minutes after death a crescent (see below) 
was obtained in the blood taken from a finger, and fifteen hours 
after death, during the autopsy, a few of the large pigmented intra- 
cellular forms were found in blood from the spleen. 

The large pigmented intracellular bodies are the most common, and 
are always present in cases of quotidian, tertian, and quartan ague, and 
also in remittent fever aud the more irregular chronic forms. (Plate 
IV., Fig. 1.) These bodies represent a more advanced stage in the 
development of the non-pigmented forms, being larger than the 
latter and containing numerous granules of melanin, pointing to 



go CLINICAL DIAGNOSIS. 

advancing destruction of the red corpuscles. In fresh specimens these 
granules, which often assume the form of little rods, resembling 
bacteria, exhibit very active molecular movements, attracting atten- 
tion at once. The body proper is hyaline and may be seen to un- 
dergo amoeboid movements, but which are not nearly so active as 
those noted in the non-pigmented form. The movements, moreover, 
are not so readily seen, owing to the presence of the granules, which 
at first sight appear to be scattered irregularly throughout the red 
corpuscle, and only with a great deal of care, and, at times, only 
after staining, is it possible to demonstrate that these granules are 
contained in the organism. The size of these pigmented intracellular 
bodies varies considerably, some, as those described above, being very 
small, while others occupy almost the entire corpuscle. The num- 
ber of granules varies likewise, standing in a direct relation to the 
extent of corpuscular destruction. In those in which this process 
has advanced farthest nothing is seen of the original corpuscle but 
an indistinct shell containing the parasite. 

Segmenting bodies (Plate IV., Fig. 4) are observed in the blood 
of malarial patients just prior to and during the chill, and, if speci- 
mens be obtained at this time, it is frequently possible to observe 
directly the manner in which segmentation takes place. Organisms 
are then seen in which the destruction of the red corpuscle has ad- 
vanced to a stage where it is no longer possible to make out any re- 
mains of the corpuscle, the body of the parasite at the same time 
becoming granular in appearance. The melanin-granules, moreover, 
which until then have exhibited pronounced molecular movements, 
become quiescent, larger, and rounder, and gradually collect in the 
centre of the body, where they form a roundish mass in which the 
individual components can scarcely be made out. While this change 
in the position of the pigment is taking place a segmentation of the 
surrounding granular protoplasm will be observed, being most marked 
at first at the periphery, from which delicate lines converge toward 
the central mass, dividing up the protoplasm into a number of oval 
bodies, the sporules very much resembling in appearance the petals 
of a flower. The number of these sporules appears to vary with 
the type of the ague, being greater in the tertian than in the quartan 
form. In the latter, which is rare in our latitudes, only from six to 
twelve are found, according to Golgi, while in tertian ague they num- 
ber from fifteen to twenty. According to personal observations, 
however, the number varies in one aud the same specimen. In one 



PLATE IV 



FIG. 1. 



C3 






J?" 









*r* 



# «• 

r* & 






15 






Malarial Parasites : Large pigmented intracellular form. 

The destruction of the red corpuscle is already well 

advanced. Taken from a case of tertian ague. 

Unstained specimen.) 




Malarial Parasites : Crescents and 
ovoids. Taken from a case of chronic 
malaria. Some of the organisms are 
provided with a bib. (Unstained spe- 
cimen.) 



FIG. 








Malarial Parasites : Flagellate form and free flagella. Taken 
from a case of tertian ague during the chill. 
Unstained specimen.) 



Malarial Parasites : Segmenting 
bodies and free "spores"; gomeof 
the latter are provided with a (.il- 
lium. Taken from a case of ter- 
tian ague during the height of 
the chill. (Unstained specimen.) 



THE BLOOD. 81 

case of quotidian ague as lew as eight and as many as seventeen were 
counted. Still later the entire body of the parasite appears to be 
rilled with these little oval sporules, scattered in an irregular manner, 
and it is frequently possible to observe a tiny dot at that end of each 
which was originally directed toward the periphery. Sometimes 
this appearance is observed during the petal stage. The apparent 
envelope of the parasite then disappears and the sporules lie free in 
the blood. An expulsion of the sporules, as though the envelope 
had been burst asunder, is often seen, when they may move about 
for a time in an active manner, and in two cases observed it was 
thought that a cilium could be made out at one end. 

The ultimate fate of these little bodies is as yet unknown, but it 
is likely that they in turn invade new corpuscles, cause their destruc- 
tion, and become segmented, thus giving rise to a new generation. 
As the process of segmentation, moreover, coincides in time with the 
occurrence of the chill, it would appear that the interval elapsing 
between two consecutive chills— i. e ., the type of the ague — depends 
upon the rapidity with which the non-pigmented forms arrive at 
maturity. 

In the more chronic forms of malaria the non-pigmented and pig- 
mented intracellular organisms are also found ; in addition to these 
curious erescentic bodies are seen, which do not appear to bear any 
relation to the former. (Plate IV., Fig. 2.) To this form the name 
Laveriana malaria? has been applied by Grassi and Feletti. It is 
still an open question whether or not these bodies actually represent 
a stage in the life-history of the organism met with in the typical 
acute varieties of ague. 

The typical crescents are highly refractive bodies, somewhat larger 
than the red corpuscles and measure about 2 // in their transverse 
diameter. Their extremities are usually rouuded off and joined 
by a delicate curved line, bridging over their concave border. Like 
the large intracellular forms these are also pigmented, the little rods 
or granules of melanin generally being found collected about the 
centre of the body ; occasionally they are seen near one extremity. 
While usually quiescent, a migration of some of the granules toward 
one extremity and back to the central mass may at times be observed. 
Occasionally specimens are seen in which the little band by some 
supposed to represent the remains of the red corpuscle is found 
along the convex instead of the concave border. 

In addition to the typical crescents, ovoid and spherical bodies 

6 



82 CLINICAL DIAGNOSIS. 

(Plate IV., Fig. 2) showing the same general features as the former, 
and often likewise provided with a little hood, are also seen in the 
more chronic forms of malaria. To judge from personal observa- 
tions these represent transition-forms between the large pigmented 
intracellular organisms and the crescents proper. 

Both in the acute and chronic forms organisms of an oval or 
circular form are seen, which are somewhat smaller than a red cor- 
puscle and provided with from one to six flagella. (Plate IV., Fig. 
3.) Attention is first drawn to these bodies by certain disturbances 
noticeable among the red corpuscles, which are caused by the whip- 
ping movements of the flagella. Their presence in the blood of 
malarial patients is conclusive of the true character of the plasmodia, 
and in Laveran's first communication their description attracted 
much attention. In these the melanin-granules are generally found 
collected excentrically within the parasite and presenting rapid 
molecular movements rarely observed in other forms. The flagella 
themselves are extremely slender filaments issuing from one or more 
points on the periphery, and presenting minute enlargements here 
and there in their course. Their length varies, as a rule not exceed- 
ing the diameter of five to eight red corpuscles ; much longer 
specimens are sometimes seen, extending beyond the field of the 
microscope (one-twelfth oil immersion). 

Occasionally one of these flagella may be seen to become detached 
from the body of the parasite and to move about among the red cor- 
puscles in a rapid snake-like manner. In microscopic specimens 
they gradually come to a rest, and often curl into a spiral. (Fig. 24.) 

That error should ever happen in distinguishing such detached 
flagella from the spirilla of relapsing fever seems very improbable, 
as the true nature of these formations is shown by the presence or 
absence of other forms of the malarial organism. 

The origin of these flagellate bodies is as yet unknown, but in 
all probability they are directly derived from the ordinary non- 
pigmented intracellular form. 

In acute and chronic malaria small pigmented extracellular bodies 
are quite constantly met with, which appear to be derived from the 
large intracellular forms by a process of simple extrusion. 

Melansemia. 

Mention has repeatedly been made of the presence of melanin in 
the blood. The occurrence of leucocytes containing such granules 



PLATE V. 



FIG. 1. 



& 






%< 




Blood containing granules of melanin, some of which are enclosed in 
leucocj'tes and some occurring free in the blood. Taken from 
a case of chronic malaria. (Unstained specimen.) 

FIG. 2. 




Bacteria of the Mouth. (Cornil Babes. 



FIG. 3. 




Leptothrix Buccalis. (v. Jaksch. i 



THE BLOOD. 



83 



should always excite suspicion of malarial disease and lead to a 
careful examination, as a melan;eniia has so far only been observed 
in this disease, in relapsing fever, aud in connection with the rare 
melanotic tumors, in which not only leucocytes containing melanin 
occur in large numbers, but also masses of this pigment float free 
in the blood. (Plate V., Fig. 1.) 

Two parasites still remain to be considered, the filaria sanguinis 
homiuis and the distoma haematobium, both of which are rarely 
seen in our latitudes, but occur endemically in tropical and sub- 
tropical countries. 

Filaria Sanguinis Hominis (Filaria Bancrofti). 

The filaria sanguinis hominis (Fig. 24) belongs to the class of 
nematode annelides. The female, according to Manson's description, 
is " a long, slender, hair-like animal, quite three inches in length, 

Fig. 24. 




Filaria sanguinis hominis. (Musser, after Lewis.) 

but only one one-hundredth inch in breadth, of an opaline appearance, 
looking as it lies in the tissues like a delicate thread of catgut, ani- 
mated aud wriggling. A narrow alimentary canal runs from the 
simple club-like head to within a short distance of the tail, the re- 
mainder of the body being almost entirely occupied by the repro- 
ductive organs. The vagina appears about one twenty-fifth of an 
inch from the head ; it is very short and bifurcates into two uterine 
horns, which, stuffed with embryos in all stages of development, run 
backward nearly to the tail." (Osier.) The male worm is rarely 
seen, and is much smaller than the female. While the adult para- 
site has its habitat in the lymphatics, the embryos, which are set free 
in enormous numbers, invade the blood-current, in which they may 
readily be found at night ; during the day an examination of the blood 



84 CLINICAL DIAGNOSIS. 

will usually yield negative results. This periodicity may, however, be 
reversed by having the patient sleep in the daytime and be about at 
night. Each embryo has an envelope of its own, which is hyaliue 
in appearance aud within which the young worm, measuring 0.34 
mm. in length by 0.0075 mm. in breadth, is able to extend aud con- 
tract itself. In fresh preparations these organisms are readily detected 
by the disturbance which their movements create among the corpuscles, 
when they are apparently transparent and homogeneous, but after 
some time, when the worm has come to rest, it will be seen that 
they are granular and transversely striated. 

As the presence of these parasites usually in itself does not produce 
symptoms, and as an examination of the blood made in daytime, as 
already stated, generally yields negative results, attention is only 
drawn to their presence when symptoms pointing to an occlu- 
sion somewhere in the course of the lymphatic channels exist, as 
evidenced by chyluria (which see), elephantiasis, or lymph scrotum. 

Distoma Haematobium (Bilharzia Hsematobia). 

The distoma haematobium belongs to the class of trematode pla- 
todes, and has never been met with in the United States or in 
Europe. According to Bilharz, the greater portion of the Fellah 

Fig. 25. 




Distoma hfemotobium, Male and female, with eggs. (V. Jaksch.) 

and Coptic population of Egypt is infected by it, giving rise to diar- 
rhoea, hematuria, and ulceration of the mucous surfaces. The male 
is smaller but thicker than the female, measuring from 12 tol4 mm. 
in length ; on its abdominal surface a deep groove is found with over- 
lapping edges, which serves for the reception of the female. (Fig. 25.) 
While the adult parasite is but rarely seen in the blood, its ova 
are frequently detected. These are slender bodies, measuring 0.12 
mm. in length by 0.04 mm. in breadth, and provided with a distinct 
little spike-like projection, issuing from one extremity or the side. 



THE BLOOD. 



85 



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CHAPTEK II. 

THE SECRETIONS OF THE MOUTH. 

SALIVA. 

Normal saliva is a mixture ol secretions derived from the sub- 
maxillary, sublingual, parotid, and mucous glands of the mouth. It 
is a colorless, inodorous, tasteless, somewhat stringy and frothy liquid, 
and serves the purpose of aiding in the acts of mastication, deglu- 
tition, and digestion. Its amount per diem varies from 600 to 1200 
grammes. 

General Characteristics. 

Normal saliva has a specific gravity of from 1.002 to. 1.009, cor- 
responding to the presence of from 4 to 10 grammes of solids. Its 
reaction is usually slightly alkaline ; it may, however, become acid 
at times, when lactic acid fermentation takes place in the mouth. 
This acid, according to Magittot, corrodes the enamel of the teeth, 
and may ultimately produce dental caries. 

Chemistry of the Saliva. 

In order to give an idea of the general composition of this secre- 
tion the following analyses are appended, the figures corresponding 
to 1000 parts by weight of saliva : 



Water 


995.2 


994.20 


988.1 


Ptyalin 1 


1.34 


1.30 


1.3 


Mucin ) 
Epithelium ) 


1.62 


2.20 


2.6 








Fatty matter .... 






0.5 


Sulphocyanides 


0.06 


0.04 


0.09 


Alkaline chlorides . 


0.84 






Disodium phosphate 


0.94 


2.20 


3.4 


Magnesium and calcium salts 


0.04 






Alkaline carbonates 




. . . 





1 These figures are too high, as they refer to the total precipitate obtained with alcohol. 






////: shVIik'TIONS OF THE MOUTH. 87 

la order to demonstrate the presence of the snlphocyanides it is 
usually only necessary to heat a few CO. of the pure saliva, faintly 
acidified with muriatic acid, with a dilute solution of perohloride of 
iron, when a red color will be seen to develop. If necessary, larger 
quantities, such as 100 c.c, are evaporated, and the test applied to 
the concentrated fluid. Of organic matter a little albumin, mixed 
with mucin, and about 1 gramme of urea per litre are found. Of 
all these substances, the ptyalin is especially interesting from a 
physiologic point of view. It may be prepared in a pure state, 
according to Gautier's method : 

To a large quantity of saliva 98 per cent, alcohol is added as long 
as a flocculent precipitate is seen to form. This is collected upon a 
small filter and dissolved in a little distilled water. The solution 
thus obtained is treated with several drops of a solution of bichlo- 
ride of mercury, in order to get rid of albuminous material, which 
is filtered off. The excess of mercury is removed by means of sul- 
phuretted hydrogen, when the remaining liquid is evaporated at a 
temperature of from 35° to 40° C, and taken up with strong alcohol. 
The insoluble residue is then dissolved in a little water, filtered, dial- 
yzed in order to remove inorganic salts, and finally precipitated with 
strong alcohol, when ptyalin will separate out in light flakes. 
Obtained in this manner ptyalin is a white, amorphous substance, 
soluble in water, dilute alcohol, and glycerine. In neutral or even 
slightly alkaline solutions, but not in acid solutions, ptyalin rapidly 
transforms boiled starch into dextrin and sugar at a temperature of 
from 35° to 40° C. This transformation takes place according to 
the equation : 

10C 6 H ]0 O 5 + 4H 2 = 4C 12 H 22 11 + C 6 H 10 O 5 + C 6 H 10 O 5 
Starch. Maltose. Achroodextrin. Erythrodextrin. 

In order to test for ptyalin more rapidly, a few c.c. of saliva are 
filtered and added to a solution of starch ; the mixture is placed in 
the warm chamber for some time, wheu it is tested with sulphate of 
copper or iodine. At first, starch gives a blue color with iodine ; 
after the reaction has proceeded further a red or violet-red color 
is obtained, indicating the presence of erythrodextrin, but no 
color at all results when achroodextrin only is present. The 
maltose may be recognized by the fact that it turns the plane of 
polarization more strongly to the right than glucose ; it also reduces 
Fehling's solution, and may thus be recognized in the absence of 
glucose. 



88 



CLINICAL LI A GSOSIS. 



Microscopic Examination of the Saliva. 

If normal saliva be allowed to stand, two layers will be seen to 
form, viz., an upper clear and a lower cloudy layer, which latter 
contains certain morphologic elements. Among these salivary cor- 
puscles, epithelial cell.-, and micro-organisms are found. (Fig. 26.) 



Fig. 26. 




^/>: r 

■« )'!/> 




Buccal secretion .eye-piece in., obj. Reichert. 1 15, homogeneous immersion : Abbe's mirror, 
open condensers'. Friedlander's and Giinther's method (V. Jaksch). a, epithelial cells; 
, salivary corpuscles ; c, fat-drops ; d, leucocytes ; e, spirochseta buccalis ; /, comma -bacillus of 
mouth ; g, leptothrix buccalis ; h, i, k, various fungi. 



The salivary corpuscles resemble white corpuscles very closely, 
but differ in their greater size and coarser appearance. The epi- 
thelial cells found in the saliva are large irregular, polygonal cells, 
provided with well-defined nuclei and nucleoli ; they exhibit certain 
irregularities in size according to their origin, and belong to the 
class of pavement or stratified epithelium. 

Of micro-organisms bacteria only are normally fouud in the saliva 
(Plate V., Fig. 2), schizomycetes and moulds, if present, being 
always derived from iugested food ; the bacteria, on the other hand, 
are present in large numbers. Bearing in mind the fact that the 
invasion of the body by disease occurs to a great extent through 
the mouth, the bacteriologic portion of this subject is especially 
interesting. Although much good work has been done in this line, 
the field has not been sufficiently worked to furnish results of much 
practical utility. 

Among the bacilli which have so far been studied in the mouth. 
some of which possess pathogenic properties, the following may be 
mentioned : 



THE SECRETIONS OF THE MO I -Til. S<) 

Leptothrix buccalis, vibrio buccalis, spirocheeta dentium, micro- 
coccus tetragenus, micrococcus hydrophobia?, micrococcus septicaemia 
sputi, bacillus carioi dentium, staphylococcus pyogenes albus and 
aureus. Under pathologic conditions o'idium albicans, actinomyces, 
the bacillus tuberculosis, and the pneumococcus may farther be found. 
The more important ones of these, and those which are oi' interest 
pathologically, will be considered later on. 

Pathologic Alterations. 

It has been mentioned that from 600 to 1200 c.c. of saliva are 
secreted in the twenty-four hours. This quantity varies under 
certain conditions. Thus an increase is frequently noted in preg- 
nancy, in various neurotic conditions, in inflammatory diseases of 
the mouth, in dental caries, following the administration of pilocar- 
pi, in poisoning with mercury, acids, and alkalies. The quantity 
is diminished in all febrile diseases, in diabetes, and often in 
nephritis. The effect of psychic emotions upon the secretion of 
saliva as well as of other glands is well known, an increase or 
a decrease in the flow being produced under various conditions. 

Among qualitative changes may be mentioned an increase in the 
amount of urea, which has been repeatedly observed, especially in 
nephritic disease. 

Urea may be demonstrated as follows : The saliva is extracted 
with alcohol, the filtrate evaporated, and the residue dissolved in 
amyl alcohol. This is allowed to evaporate spontaneously, when 
crystals of urea will be seen to separate out, which may be examined 
microscopically and chemically. (See Urine.) 

Bile-pigment and sugar have thus far never been found in the 
saliva. 

Of drugs, potassium iodide and potassium bromide rapidly pass 
into the saliva. Upon this property of the former the indirect exam- 
ination of the gastric juice as to its digestive power — i. e., the presence 
or absence of free muriatic acid — by means of the potassium iodide 
and fibrin packages of Giinzburg, is partly based. 

In order to test for potassium iodide strips of filter-paper moist- 
ened with starch solution are immersed in the saliva acidified with 
nitric acid : in the presence of potassium iodide the starch-paper 
will turn blue. 



90 



CLINICAL DIAGNOSIS. 



The Saliva in Special Diseases of the Mouth. 

Catarrhal Stomatitis. In this affection the quantity of saliva is 
increased. Microscopically an increased number of epithelial cells 
and many leucocytes are noted, their number depending upon the 
intensity of the morbid process. 

Ulcerative Stomatitis. In this condition following mercurial 
poisoning or scurvy the same appearance is noted microscopically 
as in simple stomatitis. In addition there may be observed necrotic 
tissue, red blood-corpuscles, and innumerable leucocytes. The reac- 
tion of the saliva is intensely alkaline, its color markedly brown, 
and its odor fetid. 

Thrush. O'idium albicans (Fig. 27) is mostly observed in children, 
but may also occur in adults, especially in phthisical individuals, 
sometimes lining the whole mouth. If in such a case a bit of the 
membrane be pulled off and examined microscopically, it will be 
found to consist of epithelial cells, leucocytes, and granular detritus, 



Fig. 27. 




: "■;■ 



O'idium albicans, the vegetable parasite of muguet or thrush. 
(Reduced from Ch. Robix.) 



with a network of branching, band-like formations, which present 
distinct segments. The contents of the segments are clear, and 
usually contain two highly refractive granules — the spores, one of 
which is situated at each pole. These segments diminish in size to- 
ward the end of each band, their contents at the same time be- 
coming slightly granular. 



THE SECRETIONS OF THE MOUTH. 91 

TARTAR. 

In a bit of tartar scraped from the teeth actively moving spiro- 
chsetoe are seen, as well as long, usually segmented bacilli, frequently 
forming true bands which are colored bluish-red by a solution 
of iodo-potassic iodide. The leptothrix buccals, shorter bacilli, 
which are not colored by the above reagent, micrococci, and a large 
number of leucocytes and epithelial cells which have undergone 
fatty degeneration, are also found. 

COATING OP THE TONGUE. 

A brown coating of the tongue is often observed in severe infectious 
diseases, consisting of remnants of food and incrusted blood. 
Microscopically, in addition to a large number of epithelial cells, 
enormous numbers of micro-organisms and a large number of dark 
cell-like structures, probably derived from desquamated epithelial 
cells, are found. The white coating of the tongue contains epithelial 
cells in large numbers, many micro-organisms, and a few salivary 
corpuscles. 

COATING OP THE TONSILS. 

Pharyngomycosis Leptothrica. 

In the props occasionally met with in the crypts of the tonsils in 
cases of follicular tonsillitis, as also in persons who have had fre- 
quent attacks of tonsillitis, according to Chiari, epithelial cells and 
long segmented fungi — the leptothrix buccalis (Plate V., Fig. 3) — 
which are colored bluish-red with a solution of iodo-potassic iodide, 
are seen. At times patches composed of these fungi extend over a 
considerable area of the tonsils, so that it may be doubtful whether 
or not the disease be a beginning diphtheria. A microscopic exami- 
nation, however, will in such cases settle all doubts. 

Diphtheria. 

Recognizing the great importance of an early diagnosis in such a 
dreaded disease as diphtheria, an examination for Loffler's bacillus 
in doubtful cases has become just as important to-day as that for the 
bacillus of tuberculosis, and every physician should make himself 
familiar with the methods employed for its recognition. 



92 CLINICAL DIAGNOSIS. 

By means of a sterilized, stout platinum loop, or a pair of forceps, 
a piece of membrane is scraped from the tonsils, the soft palate, or 
the pharynx and at once transferred to a sterilized test-tube, closed 
with a pledget of cotton. A particle of the membrane is then spread 
iu as thin and uniform a layer as possible, upon a cover-glass, by 
means of the platinum loop or forceps, which have been previously 
passed through the flame of a Bunsen burner. When dry the speci- 
men is fixed by being passed through the flame three or four times, 
when it is ready for staining. For this purpose L6ffler ? s alkaline 
solution of methylene-blue, which consists of 30 c.c. of a concen- 
trated alcoholic solution of methylene-blue in 100 c.c. of an aqueous 
solution of potassium hydrate (1 : 10,000), may be advantageously 
employed, the specimen being stained from five to ten minutes. It 
is then rinsed in water, placed on a slide, the excess of water 
removed with filter paper, and examined with a one-twelfth oil- 
immersion lens. 

A dahlia methyl-green solution may likewise be employed. This 
consists of 10 grammes of a 1 per cent, aqueous solution of dahlia- 
violet and 30 grammes of a 1 per cent, aqueous solution of methyl- 
green. The specimen is stained from one to two minutes. 

If it is desired to employ Gram's method, the specimen is most 
conveniently stained for three minutes with a freshly prepared con- 
centrated alcoholic solution of gentian-aniline water. This is prepared 
by adding aniline oil to 10 c.c. of distilled water, drop by drop, thor- 
oughly shaking after the addition of each drop, until the solution 
becomes opaque. It is then filtered and treated with 10 c.c. of 
absolute alcohol and 11 c.c. of a concentrated alcoholic solution of 
gentian-violet. The specimen is decolorized in a solution composed 
of 1 gramme of iodine and 2 grammes of potassium iodide, dissolved 
in 300 c.c. of water. After remaining in this solution for five min- 
utes the specimen is rinsed in alcohol, and the process repeated until 
the violet color disappears. It is then transferred to absolute alco- 
hol, oil of cloves, and mounted in balsam. 

Cultures should also be made, preferably upon a mixture of blood- 
serum and bouillon, as recommended by Loffler. This is composed of 
three parts of blood-serum aud one part of bouillon, containing 10 
per cent, of peptone, 3 per cent, of grape-sugar, and 0.5 per cent, of 
sodium chloride, the mixture being solidified in the usual manner. 
Upon this medium Loffler's bacillus grows so much more rapidly 
than other organisms usually present in the secretions of the mouth 



THE SECRETIONS OF THE MOUTH. 93 

and throat that at the end oi twenty-four hours they often form the 
only colonies that attract attention. Should other colonies of similar 
size be present these are generally quite different in appearance. In 

this manner a diagnosis ran usually be made upon the day follow- 
ing the inoculation of the tube. 

In the absence of blood-serum bouillon, alkaline bouillon, nutrient 
gelatin, nutrient agar, glycerine-agar, and potato may be employed. 
Coagulated egg-albumin, as pointed out by Booker, and milk are 
also good soils. 

The colonies are large, round, elevated, and grayish-white in 
color, with a centre that is more opaque than the slightly irregular 
periphery. The surface of the colony is at first moist, but after a 
day or two has a dry appearance. 

The bacillus (Fig. 28) is non-motile and varies in size and shape, 
its average length being from 2. 5 fi to S jut, its breadth from 0.5/i to 

Fig. 28. 

y 5 or -c, 
1 .•— 

4 "*> , » # 

f r - *- 

a 

Bacillus of diphtheria, (Abbott. ) 
a. Its morphology when cultivated on glycerine agar-agar. b. Its morphology as seen in 
cultures on Liiffler's blood-serum. 

0.8 fi. Its morphologic characteristics are so peculiar as to render 
its identification upon cover-slip preparations and in sections of 
the diphtheritic membrane an easy matter in most cases. 

Sometimes the organism appears as a straight or slightly curved 
rod ; especially characteristic are irregular and often bizarre forms, 
such as rods with one or both ends terminating in a little knob, 
and rods broken at intervals, in which short, well-defined round, 
oval, or straight segments can be made out. 

Some forms stain uniformly, others in an irregular manner, the 
most common present the appearance of deeply stained granules in 
faintly stained bacilli. 

Streptococci are also seen, as a rule, and it may be said that the 
gravity of a case is directly proportionate to the number of strepto- 
cocci present. 




CHAPTEE III. 

THE GASTRIC JUICE AND GASTRIC CONTENTS. 

THE SECRETION OF GASTRIC JUICE. 

The gastric juice is the result of the glandular activity of the 
stomach, and the only secretion of the digestive tract which presents 
an acid reaction. 

As is well known, the mucous membrane of the stomach is 
covered throughout its entire extent by a single layer of cylindrical 
epithelium, which dips down in places to line the orifices and larger 
ducts of the numerous tubular glands with which it is beset. Of 
these latter, two kinds have been described, viz., the fundus and 
pyloric glands, so named from the locatiou at which they are princi- 
pally found. In the secretory portion of a fundus gland two different 
sets of cells can be distinguished, one being small, granular, and 
polyhedral or columnar, bordering upon the narrow lumen of the 
tube, termed chief or principal cells by Heidenhain ; they are also 
known as central or adelomorphous cells. These stain with ani- 
line-dyes to only a slight extent. The others, known as parietal, 
delomorphous, or oxyntic cells, are variously situated between the 
adelomorphous cells and the membraua propria, being most numer- 
ous in the necks of the glands. They are larger than the chief cells, 
oval or angular and finely granular structures, possessing a strong 
affinity for the aniline-dyes. The pyloric glands, which are found 
only in the region of the pylorus, on the other hand, are character- 
ized by the greater length of their ducts, which are also lined by 
the cylindrical epithelium of the mucous membrane proper. The 
secretory portion of these glands is represented by a single layer of 
short and finely granular, columnar cells, which closely resemble the 
chief cells of the fundus glands. In addition to these a few isolated 
cells, the cells of Nussbaum, are found, which in structure and in 
their behavior to aniline-dyes resemble the parietal cells. 






THE GASTRIC JUICE AND GASTRIC CONTENTS, 95 



Upon chemical examination the gastric juice is seen to consist 
essentially of water, free hydrochloric acid, pepsin, rennet (a milk- 
curdling ferment), mucus, and certain mineral salts. 

Of these, free hydrochloric acid is secreted by the parietal cells, 
pepsin and the milk-curdling ferment by the chief cells of the fundus 
and the pyloric glands, while the mucus is the product of secretion 
of the cylindrical goblet-cells lining the stomach and the wider por- 
portions of its glandular ducts. 

It must be borne in mind, however, that the ferments mentioned do 
not exist in the cells as such, but as zymogens, which are transformed 
into the ferments through the activity of the free hydrochloric acid. 
According to modern investigations, moreover, the zymogens only 
are secreted by the cells. 

Until recently it was generally supposed that the gastric juice is 
only secreted upon appropriate stimulation of the nervous mechan- 
ism of the stomach either directly or indirectly, and that the stom- 
ach in its quiescent state — i.e., when not digesting — is empty. The 
researches of Schreiber and Martius, however, have rendered the 
correctness of this view very doubtful, as they were able to obtain 
quantities of gastric juice, varying from 1 to 60 c.c, from the non- 
digesting stomach of every normal person examined. 

To those who consider the gastric juice a digestive fluid, and 
believe the furnishing an antiseptic secretion one of the functions — 
probably the principal one — of the stomach, a continuous secretion is 
not surprising. 

Further observations are necessary in order to decide as to the 
correctness of Schreiber's teachings. It may be said, however, that 
his experiments are more free from objection and possess more 
merit than those generally brought forward in support of the view 
previously held. 

TEST-MEALS. 

Although Schreiber appears to have demonstrated that the secre- 
tion of gastric juice takes place continuously, the amount that can 
usually be obtained from the non-digesting organ is not sufficient 
for analytical purposes. It is, therefore, necessary to stimulate the 
glandular apparatus of the stomach to increased activity. This may 
be accomplished with thermic, chemical, electric, and digestive stim- 
uli, among which the last named are the most convenient and the 



96 CLINICAL DIAGNOSIS. 

most effective, furnishing a picture not only of the chemical, but 
also of the motor and resorptive activity of the organ. The analyt- 
ical results will, however, depend to a large extent upon the character 
of the food ingested, starches and fats exerting but a slight stimulating 
effect, while proteids cause a copious secretion of gastric juice. The 
ingestion of fluids at the same time will likewise influence the results 
obtained, owing to the dilution of the gastric juice. The time of 
the height of digestion, moreover, varies with the kind aud quan- 
tity of food taken. In order to obtain uuiform results it is, there- 
fore, necessary to withdraw the gastric contents at a certain period 
after the ingestion of a meal of known composition aud bulk. 

[Numerous test-meals have been proposed. The following are the 
most important : 

The Test-breakfast of Ewald and Boas. 

This consists of from 35 to 70 grammes of wheat-bread and from 
300 to 400 c.c. of water or weak tea without sugar. It is best to 
give this meal to the patient early in the morning when the stomach 
is empty — i. e., as a breakfast. The gastric contents are obtained 
one hour later. 

The Test-dinner of Riegel. 

This consists of a plate of soup (400 c.c), a beefsteak (200 
grammes), a slice or two of wheat-bread (50 grammes), and a glass- 
ful of water (200 c.c). The contents of the stomach art. obtained 
after four hours. The great disadvantage of this method lies in the 
fact that the lumen of the stomach-tube is frequently occluded by 
large pieces of undigested meat, a source of annoyance which may 
be guarded against by making use of finely chopped meat. 



The Double Test-meal of Salzer. 

For breakfast the patient receives 30 grammes of lean, cold 
roast, hashed or cut into strips sufficiently small not to obstruct 
the stomach-tube, 250 c.c. of milk, 60 grammes of rice, and one 
soft-boiled egg. Exactly four hours later the second meal is taken, 
consisting of 35-70 grammes of stale wheat-bread and 300-400 c.c. 
of water. The gastric contents are withdrawn one hour later. In 
this manner the gastric juice is not only obtained at the height of 
digestion, but an idea may at the same time be formed of the motor 






THE GASTRIC JUICE AND GASTRIC CONTENTS. 97 



power of the stomach. Under normal conditions the organ should 
contain no remnants ol the first meal at the time of examination. 

The Test-breakfast of Boas. 

This consists of a platei'ul of oatmeal-soup, prepared by boiling 
down to one pint a quart of water to which one tablespoonful of 
rolled oats has been added. A little salt may be used if desired, 
but nothing more. The contents of the stomach are obtained one 
hour later. This test-meal was devised by Boas in order to guard 
against the introduction from without of lactic acid, which is present 
in all kinds of bread. The meal is employed in doubtful cases of 
cancer of the stomach, in which a quantitative estimation of lactic 
acid is to be made, the stomach being washed out completely the 
night before. 

Still other test-meals have been suggested, but they do not present 
any material advantage over those described. 

THE STOMACH-TUBE. 

The stomach-tubes which are now generally in use are essentially 
large Xelaton catheters. They should measure at least 72 to 75 
cm. in length, and be provided with three fenestra, of which one 
is placed at the end of the tube and two laterally, as near the end 
as possible. For the purpose of washing out the stomach the tube 
is connected with a glass funnel by means of ordinary rubber tubing, 
which can be detached from the stomach-tube proper. There is no 
advantage in rubber funnels or in having a continuous tube. 

It is important that the tubes should be thoroughly cleansed in 
hot water as soon after use as possible. The advice of Boas, more- 
over, to have special marked tubes for tuberculous, syphilitic, and 
carcinomatous patients should be borne in mind. Patients in whom 
lavage is to be practised for any length of time should provide their 
own instruments. 

CONTRAINDICATIONS TO THE USE OF THE TUBE. 

Of direct contraindications to the use of the tube there should be 
mentioned the existence of the various forms of valvular disease 
when in a state of imperfect compensation, angina pectoris, arterio- 



98 CLINICAL DIAGNOSIS. 

sclerosis of high degree, aneurism of the large arteries, recent hemor- 
rhages from whatever cause, marked emphysema with intense bron- 
chitis, acute febrile diseases, etc. 

THE INTRODUCTION OP THE TUBE. 

The technique of the introduction of the tube should be as simple 
as possible ; the exhibition of complicated bottle-apparatus for the 
purpose of obtaining the gastric juice only adds to the excitement of a 
nervous patient, and should be avoided. The patient's clothing and 
floor of the room should be protected from being soiled by material that 
may be vomited along the sides of the tube, the dribbling of saliva, etc. 
For this purpose Turcks' rubber bib with pouch may be advan- 
tageously employed. " It is so arranged as to form a pouch in front 
to catch the saliva or stomach-contents that may be thrown off from 
the mouth or stomach. A detachable tube passes from the bottom 
of the pouch and is conducted into a basin or any vessel." 1 

Cocainization of the pharynx is rarely necessary, but may be re- 
sorted to in hypersesthetic individuals, a 10 per cent, solution being 
employed. 

The tube, held like a pen, is introduced to the posterior wall of 
the pharynx, the patient bending his head forward, and not back- 
ward, as is usually done. The patient is then told to swallow, 
but this is not absolutely necessary. The tube is pushed on 
until resistance is felt when it meets with the floor of the stomach. 
During the entire process, which does not occupy ten seconds, the 
patient should be instructed to look into the eyes of the operator. 
As long as he is able to do so everything is well. At the least sign 
of cyanosis, or of marked pallor, the tube should be at once withdrawn 
and the patient observed for a day or two before a second attempt is 
made. 

If the gastric juice does not flow at once, the patient is instructed 
to bear down with his abdominal muscles, and, if this be insufficient, 
to cough a little. Repeated attempts of this kind will usually 
bring about the desired result, unless the tube has not been intro- 
duced far enough or too far ; in the latter case it will double upon 
itself, so that its end may actually stand above the level of the 
liquid. (Method of expression.) 

1 Manufactured by G. Tiemann & Co., Philadelphia. 






Fig. 29. 



THE GASTRIC JUICE AND GASTRIC ( 'ONTENTS. 99 

Rarely, aspiration must be resorted to. For this purpose Boas's 
bulbed tube (Fig. 29) is most convenient. The manner in which it 
is used is as follows : The proximal end of the tube, after having 
beeD introduced into the stomach, is com- 
pressed and the bulb squeezed, when the 
distal end is clamped aud the bulb al- 
lowed to expand. In this manner a 
partial vacuum is produced in the tube, 
which usually causes a flow of gastric 
juice. In the absence of such an in- 
strument the stomach-tube may be con- 
nected with a bottle in which a partial 
vacuum has been established by aspiration 
(Fig-. 30). Unless the patient is accus- 
tomed to the introduction of the tube 
these more complicated appratus should be 
avoided as much as possible. (Method of 
aspiration.) 

In order to icash out the stomach the 
fuunel-tube is attached, the funnel filled 
with lukewarm water or any desired 
medicated solution, elevated to a height 
somewhat above the head of the patient, 
aud the water allowed to flow. From 
500 to 1000 c.c. may be introduced at 
one time. By suddenly depressing and 
inverting the funnel, over a suitable ves- 
sel, before all water has left the funnel, a siphon arrangement is 
established and the stomach emptied. It is well to measure the 
returning water, as well as the amount introduced. Should the flow 
diminish or cease before all the water introduced has been removed, 
the end of the tube probably stands above the level of the liquid, 
and the flow can be started again by pushing the tube on further 
or by withdrawing it a little, as the case may be. 

Washing out the stomach soon after the ingestion of a full meal 
often proves a very tedious and annoying, if not an impossible, 
procedure, as the fenestra readily become obstructed. Should this 
occur, the funnel, filled with water, is elevated as high as possible, 
with a view to overcome the obstruction by hydrostatic pressure, 
or, if this prove insufficient, the funnel- tube is detached and the 




Boas's bulbed tube. 



100 CLINICAL DIAGNOSIS. 

Fig. 30. 




Arrangement of bottle for the aspiration of the gastric contents. 

obstruction dislodged by means of air. for which purpose a Politzer- 
bag is verv convenient. 

GENERAL CHARACTERISTICS OF THE GASTRIC 

JUICE. 

Pure gastric juice is an almost clear faintly yellowish fluid, of a 
bout taste and a peculiar characteristic odor. Its specific gravity 
varies between 1.002 and l. r responding bo the presence of 

but 0.5 per cent, of solids. Its reaction, owing to the presence of 
hydrochloric acid, is acid. 

AMOUNT. 

Very little is known of the total quantity of gastric juice secreted 
in the twentv-four hours. The figure given bv Beaumont, viz.. IS'" 1 
grammes pro die. based upon observations made upon the often- 
quoted Canadian hunter. Alexis St Martin, is undoubtedly too 
low. The amount _ vea by Bidder and Schmidt, viz.. that corre- 
sponding to about one-tenth of the body-weight, is more probably 
correct. 1 It may be stated . however, that the quantity 

secreted varies within wide limits, being influenced by numer: as 
factors, and notably by the decree of the appetite and the amount 

1 Griinewald's figure— : - . : amines— the author likewise regards as too low. The daily 
secretion appears to vary between 3X» and 3000 c.c. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 101 

and character of the food taken, especially thai of the proteids. 
Tlie age and sex of the individual, the time of day, notably in its 
relation to the ingestion of food, the emotions, etc., undoubtedly 
influence the glandular activity of the stomach. 

From the non-digesting organ, as has been pointed out, from 
1 to 60 c.c. of gastric juice may be obtained at one time. The 
amount which can be procured during the process of digestion, on 
the other hand, varies with the amount of liquid ingested, the 
time of expression, the size and motor power of the stomach, and 
the degree of transudation ; the process of resorption probably does 
not play any part, as it has been ascertained that very little water, 
if any, is absorbed by the stomach. 

According to Boas, from 20 to 50 c.c. of filtrate can be obtained 
exactly one hour after the ingestion of Ewald's test-breakfast under 
physiologic conditions. 

Abnormally large quantities of gastric juice are practically only 
found in cases of so-called hypersecretion, the " Magensaftfluss " of 
the Germans, which may occur periodically or continuously. For- 
merly the presence of gastric juice in appreciable quantities in the 
non-digesting stomach was regarded as conclusively proving the 
presence of this disease, but in the light of Schreiber's researches 
this position can no longer be maintained. The diagnosis should, 
hence, only be made when in conjunction with the clinical symp- 
toms of hypersecretion from 100 to 1000 c.c. of pure gastric juice 
can be obtained from the non-digesting organ. To this end the 
stomach should be emptied completely by the tube before retiring, 
and an examination made upon the following morning, no food or 
liquids being allowed in the meantime. 

In various pathologic conditions abnormally large quantities of 
liquid may be obtained, which cannot, however, be regarded as 
gastric juice. Attention will be drawn to these conditions at another 
place. 

CHEMICAL EXAMINATION OP THE GASTRIC JUICE. 
Chemical Composition of the Gastric Juice. 

As has been briefly shown above the gastric juice consists of water, 
free hydrochloric acid, certain ferments, their zymogens, and mineral 
salts. Analyses giving the exact chemical composition of pure, 
uncontaminated gastric juice in man are still wanting, owing to 



102 



CLINICAL LI A GNOSIS. 



the difficulty oi excluding the saliva. In patients the subjects of 
gastric fistula analytical studies have, however, repeatedly been 
made, and from the table below, taken from Schmidt, an idea may be 
formed of the various amounts of solid constituents contained in 
1000 parts of gastric juice, uncontaminated by food or the products 
of digestion, but not free from saliva : 



Water .... 










994.40 


Solids .... 










o 60 


Organic material 
Sodium chloride 










3.19 
1.46 


Calcium chloride 










0.06 


Potassium chloride 










0.55 


Ammonium chloride 












Hydrochloric acid . 










0.20 


Calcium phosphate ) 

Magnesium phosphate - 0.12 


Iron phosphate ' 













The Acidity of the Gastric Juice is Referable to the 
Presence of Free Hydro chloric Acid. 

It has been conclusively demonstrated by Schmidt that the acidity 
of the gastric juice is due to the presence of free hydrochloric 
acid. After accurately determining the amount of chlorine and 
of all basic substances present, it was found that after all of the 
latter had been saturated a quantity of hydrochloric acid still re- 
mained, which in the dog varied between 0.25 and 0.42 per cent., 
with an average of 0.33 per cent. The amount of free acid was 
also determined by titration and the same results reached as by 
gravimetric analysis. 

While the acidity of pure gastric juice — i.e.. gastric juice not 
contaminated bv saliva or food in its various stages of digestion — 
is thus solely due to the presence of free hydrochloric acid, other 
factors enter into consideration in the examiuation of the gastric 
contents during the process of digestion. Acid salts and varying 
amounts of lactic acid derived from the carbohydrates of the food 
are also found. At the beginning of digestion the acidity, accord- 
ing to Ewald, is due to a certain extent to the presence of lactic acid. 1 
Hydrochloric acid, it is true, is present at the same time, but is held 
in combination by albuminous material. Later ou, when the albumi- 
noid bodies have become saturated, it appears as such, with the 

See Lactic Acid. p. 134. 



THE GASTRIC JUICE AND QASTRIi CONTENTS. 
Fig. 81. 



103 



P.M. 



.>.<> ~r 


.... 




2.5 -I 


_..... .... ,,,,,. 


-- - "j- - 


2.0 1 H — h 


I I 1 i 1 1 l 1 1 I I t 1 1 1 1 I 1 1 1 1 1 1 11 1 1 1 1 i M 1 1 ii M 1 1 ll 1 M 1 1 




1.3 ' \^-^— — ^ ^- L — 


fff] \\\\] , 


,o.==4=======;*miHi#ffT======== = ======== : 


1.2o 1 -/- — -- — — — 1 


::::: ::??:::::~:::~~: . :: :::::::::: 


w :::::::-i:::::;:::::::::::::::::::::::::::::::::::: 


1 


IZ 


ZZZ^Z _- - - -- - — - - 


075 J — I 1 1 


:::^:;zf:::::::::::-::::::::::: f ::::::::: 


o.o~+i—'— T + -r iz^r 


—fV 1 — 


It ' i i i i i 

0.25 -ff- ! 1 i!l i — ' 1-| 




f — n - ill 


~ i,,.,.. 



10 20 30 40 50 60 



80 90 100 



Diagram illustrating the curve of acidity after Ewald's test-breakfast. (Rosenheim.) 

Hydrochloric acid. Lactic acid. X Beginning of the stage of free hydrochloric 

acid. P. M. Pro mille. The numbers upon the abscissa indicate the minutes. 

Fig. 32. 



1 


P M 1 




i 


i n 
























" ~ i | " I ' """ "■ 


i 


1 Ml ^- — -v 




- 5 .,^ \ 


; ■ ■ ■ ! : m 1 .-PrT V 


s« S 


i \s\\ 1 ' s 


9 JUyi S 




1 j/\ ' ~~^ 


iT *"""'"- 


1 s 


, - K ' 1 ! 




■ f 


j< ' 


s ' rr|*H-l4i 


m ' ' ■ Ml ~"T-, 


/ / 1 




"J / 




C\ ~ / ' ~ 


u..j / y 


1 / 


I 9 


1 r\ 


fx- —|- ----- | ----- -| ■---;- :- 



30 60 90 120 150 180 210 210 270 300 



Diagram illustrating the curve of acidity after Riegel's test-breakfast. (Rosenheim.) 

Hydrochloric acid. Lactic acid, x Beginning of the stage of free hydrochloric 

acid. 



104 CLINICAL DIAGNOSIS. 

result that the formation of lactic acid progressively diminishes, 
owing to the inhibitory action on the part of the hydrochloric acid 
upon the lactic-acid-producing organisms. The varying degrees of 
acidity after such test-meals as those of Ewald and Riegel, at different 
periods of digestion, and the amount of the two acids present, may be 
seen from the accompanying diagrams (Figs. 31 and 32). 

Under pathologic conditions the amount of free hydrochloric acid, 
as will be shown, may undergo great variations, diminishing on the 
one hand to 0, and increasing on the other to 0.4 per cent., or even 
more. At the same time the amount of lactic acid, which normally 
is present in very small amounts, and is absent altogether at the 
height of digestion, may greatly increase. The presence of fatty 
acids, moreover, which are normally not present in the gastric juice, 
may also be observed in pathologic conditions. It is thus seen that 
the total acidity of the gastric juice, especially in disease, cannot be 
regarded as indicating the amount of one single acid, unless the 
absence of abnormal acids, lactic acid, and acid salts is insured. 

Method of Determining* the Total Acidity of the Gastric 

Contents. 

To this end a known quantity of gastric juice is titrated with a 
one-tenth normal solution of sodium hydrate, using phenolphthalein 
as an indicator, when the number of c.c. of the one-tenth normal 
solution employed, multiplied by the equivalent of 1 c.c. of this 
solution in terms of hydrochloric acid, will indicate the amount of 
acid present in terms of the latter, from which the percentage-acidity 
is readily calculated. 

A normal solution of sodium hydrate is one containing the equiv- 
alent of its molecular weight in grammes — i. e., 40 grammes, in 1000 
c.c. of distilled water ; a decinormal solution will therefore contain 
4 grammes in the same volume of water. This quantity is dissolved 
in less than 1000 c.c. and the solution brought to the proper strength 
by titrating a solution of oxalic acid of known strength with the 
same. 

From the equation, 

2NaOH + C 2 H 2 4 = C 2 Na 2 4 + 2H 2 0, 

it is seen that two molecules of NaOH (mol. weight 40) combine 
with one molecule of C 2 H 2 4 + 2H 2 (mol. weight 126), or 4 parts 
by weight of the former with 6.3 of the latter. One-tenth gramme 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 105 

of oxalic acid would, hence, require 15.873 c.c. of the one-tenth 
normal solution of NaOIl for its neutralization, as is apparent from 
the equations : 

6.3 : 1000 :: 0.1 : x ; 6.3* = 100 and a?= 10( ^ = 15.873. 

One-tenth gramme of pure crystallized C 2 H 2 4 is dissolved in 
distilled water, and the solution titrated with the one-tenth normal 
solution of sodium hydrate which is to be corrected, using a drop or two 
of a 1 per cent, alcoholic solution of phenolphthalein as an indicator, 
until the rose color of the solution has entirely disappeared; 15.9 c.c. 
should bring about this result. As the NaOH solution, however, 
has been purposely made too strong less will be required. The 
amount of water that must then be added in order to bring the solu- 
tion to its proper strength is determined by the formula C = — , 

in which C represents the number of c.c. of water which must be 
added to the remaining solution, N the total number of c.c. remain- 
ing after one titration, n the number of c.c. consumed in one titration, 
and d the difference between the number of c.c. theoretically required 
and that actually used in one titration. The solution having thus 
been properly diluted, the correctness of its strength is again tested 
and a further correction made, if necessary, until absolute accuracy 
has been attained. 

1000 c.c. of the one-tenth normal solution containing 4 grammes 
of NaOH are equivalent to 3.65 grammes of HC1, as is seen from 
the equation : 

NaOH + HC1 = NaCl+H 2 
40 36.5 

1000 c.c. of the yV normal solution represent 3.65 grms. of HC1. 
100 " " " " ' " 0.365 grm. " " 

10 " " " " " " 0.0365 " " " 

1 '' " " " - represents 0.00365 " " " 

Application to the gastric juice : 5 or 10 c.c. of the filtered gas- 
tric juice are titrated with the one-tenth normal solution of sodium 
hydrate, using two or three drops of a 1 per cent, solution of phenol- 
phthalein as an indicator, until the rose color which appears after the 
addition of every drop of the sodium hydrate solution no longer dis- 
appears on stirring nor becomes deeper after the addition of a further 
drop. The number of c.c. of the one-tenth normal solution employed 
multiplied by 0.00365 will then indicate the acidity of the 5 or 10 



106 CLINICAL DIAGNOSIS. 

c.c. of gastric juice in terms of HC1, from which the percentage- 
acidity is readily calculated. 

Example : 10 c.c. of gastric juice required the addition of 6.5 c.c. 
of the one-tenth normal solution ; 6.5 X 0.00365 (i. e., 0.0237) would 
hence indicate the acidity of the 10 c.c. of gastric juice in terms of 
HC1, and 0.0237 X 10 = 0.237, the percentage-acidity. 

As these figures express only the amount of HC1 in pure gastric 
juice obtained from normal individuals, it has been found more 
convenient for clinical purposes to indicate merely the degree of 
acidity by the number of c.c. of the one- tenth normal solution 
employed. 

In the above example, in which 6.5 c.c. of the latter were used, the 
percentage-acidity would thus be indicated by the figure 65 ; i. e., 
the number of c.c. of the one-tenth normal solution necessary to 
neutralize 100 c.c. of gastric juice. 

Under normal conditions such figures as 40 to 60 are usually 
found one hour after the ingestion of Ewald's test-breakfast, while 
in pathologic conditions considerable variations are observed. It 
may be stated, as a general rule, that in the acute and chronic 
inflammatory conditions of the stomach, as well as in some of 
the neuroses, the acidity of the gastric contents is below normal. 
Higher figures are met with in cases of ulcer, some cases of dilata- 
tion, and notably so in some of the neuroses, in which a degree 
of acidity corresponding to 90 or even more is not infrequently 
observed. Increased acidity, usually associated with hypersecretion 
of gastric juice, is met with in the so-called hypersecretio acida et 
continua of Reich mann. 

It has been pointed out that the reaction of normal gastric juice 
is always acid, owing to the presence of free HC1, and the same 
may be said to hold good for the gastric contents in general obtained 
from a normal individual. Pathologically an acid reaction is also 
the rule, as in those cases in which HC1 is absent fatty acids and 
lactic acid in considerable amount make their appearance. It is, 
therefore, not at all surprising that an alkaline, neutral, or ampho- 
teric reaction is but rarely, or, at least, not commonly observed, in 
the gastric contents artificially obtained, and practically seen only in 
the so-called mucous form of chronic gastritis. In vomited material 
such observations are quite common, not so much so, however, in 
the specimens first brought up as in those that are subsequently 
ejected. The vomited material in cases of so-called vomitus matutinus, 



THE CASTRIC .JUICE AM) CASTRH' CONTEXTS. 107 

which is usually referable to a chronic catarrhal condition of the 
pharynx, generally presents an alkaline reaction, owing to the fact 

that the fluid brought up is largely unchanged saliva. 

The Source of the Hydrochloric Acid. 

That the HC1 is not directly derived from the chlorides in- 
gested is shown by the fact that it is still secreted by a starving 
animal. The same point is also proved by the observations of 
Sehreiber, which go to show that the secretion of HO, as indicated 
above, is continuous, not to mention the well-known fact that 
material free from chlorine, when ingested, will cause the secretion of 
an acid gastric juice. It is apparent then that the chlorides of the blood 
must furnish the necessary chlorine, and as the pyloric glands, which 
contain no parietal cells, furnish an alkaline, and the fundus glands, 
which do contain parietal cells, give an acid secretion, it is thought that 
these parietal cells are in some manner concerned in the production 
of the HO. The exact manner in which this takes place has not 
been definitely ascertained, but it is not at all improbable that 
the HC1 results from a " Masseneinwirkuug " on the part of car- 
bonic acid, which is present in large quantities in the blood as such, 
upon the sodium chloride, and that, owing to a specific action on the 
part of the parietal cells, the hydrochloric acid is secreted into the 
ducts of the glands of the stomach on the one hand, while on the 
other the sodium carbonate formed at the same time is returned to 
the blood. 

Two factors are thus necessary in order that a normal amount of 
HC1 should be secreted ; i. e., a normal condition of the blood and 
a normal condition of the cells. Whenever the integrity of either 
of these two factors becomes impaired it is clear that an abnormal 
secretion of HC1 or none at all will result. The nervous system, 
furthermore, must be taken into consideration as a third factor, as ac- 
cording to our present knowledge normal innervation is the sine 
qua non for the normal activity of auy organ. The secretion of HC1 
is impaired whenever the nutrition of the cells of the stomach suffers, 
whether the result of inflammatory lesions, new growths, or hyper- 
semic conditions of the stomach, the effect of renal, hepatic, or pul- 
monary diseases, etc., or in consequence of central or peripheral 
nervous influences. 

In the secondary dyspepsias, then, the result of renal, hepatic, car- 
diac, or luemic diseases, etc., an examination of the gastric juice for 



108 CLINICAL DIAGNOSIS. 

free HC1 is of comparatively little value from a diagnostic point 

of view, although at the same time it may suggest valuable points 
for the dietetic treatment of such patients 

Significance of the Free Hydrochloric Acid. 

It was formerly thought that the principal function of the stomach 
was a digestive one, and that in tht j stomach, owing to the action of 
hydrochloric acid and pepsin, albumins were, to a large extent, trans- 
formed into peptones and albumoses. As pepsin is active only in 
the presence of a free acid, it was thought, moreover, that the power 
of the latter to render pepsin physiologically active constituted its 
entire held of usefulness. 

It had already been noted one hundred years ago, however, by the 
Abbe Spalanzani that pieces of meat immersed in gastric juice resisted 
the process of putrefaction for days, and when it was shown later on 
that the free mineral acids ranked among the most powerful of 
antiseptics, and that the stomach secreted an amount of free hydro- 
chloric acid sufficient to prevent the development of most of the 
putrefactive organisms, the time had come to doubt the correctness 
of the view previously held. 

Numerous experiments have been made in order to test the anti- 
septic and germicidal power of the gastric juice. Among the more 
important results achieved the following may be mentioned : The 
comma-bacillus of cholera asiatica is destroyed by the normal acid 
gastric juice, while infection results when this has been previously 
neutralized; a most important observation. The same holds good 
for numerous other pathogenic organisms which are of especial 
interest to the clinician. Anions these mav be mentioned the 
various species of streptococcus, staphylococcus pyogenes aureus, 
the bacillus of anthrax, etc. Unfortunately, however, not all species 
of pathogenic organisms are destroyed by the acid of the gastric 
juice, and the spores of some of those, moreover, that are destroyed 
are possessed of a considerable degree of resistance. This is espe- 
cially true of the tubercle of bacillus, and in many cases of the spores 
of the anthrax-bacillus. 

Those bacteria also which cause lactic acid and butyric acid fermen- 
tation resist the anti-fermentative power of the gastric juice to a 
certain extent, as may be concluded from the fact they are probably 
always present in the intestines. At the beginning of the process 
of gastric digestion, when the hydrochloric acid secreted is immedi- 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 109 

ately taken up by the albuminous bodies present, traces ol lactic acid 
can usually be demonstrated in the gastric contents ii carbo-hydro- 

chlorates have been ingested. Later on, when free hydrochloric acid 
appears, lactic acid fermentation ceases. This observation is in per- 
fect accord with the fact that the action of the lactic acid producers 
is prevented by the presence of 0.7 p.m. of free HC1. 

From what has been said it may be argued that as the principal 
function of the stomach consists in the furnishing of au antiseptic 
and germicidal fluid, under suitable conditions life could go on in the 
absence of the stomach. That this is possible has actually been 
demonstrated by Czerny, who succeeded in removing almost the 
entire organ from a dog. Five to six years later the same animal 
was killed in Ludwig's laboratory, and it was found at the autopsy 
that " near the cardia a small portion of the stomach had remained, 
surrounding a globular cavity filled with food." This dog then had 
lived for almost six years practically without a stomach, had gained 
in weight, and was to all intents and purposes as healthy an animal 
as one provided with an entire organ. In human beings the subjects 
of carcinoma of the stomach, not the entire organ, it is true, but a 
considerable portion thereof has been removed by operation, with the 
result that the patients enjoyed perfect health as far as could be 
ascertained, notwithstanding the fact that the remainder of the organ 
was incapable of secreting gastric juice. The motor power, however, 
was good. It is very probable then that the stomach, so far as the 
process of digestion is concerned, is not absolutely necessary for the 
maintenance of life. 

It has, furthermore, been demonstrated that a deficient secretion 
of HC1 is noted in all cases in which an increased degree of in- 
testinal putrefaction occurs, and while indol, phenol, and skatol, as 
well as their compounds with sulphuric acid, in the amounts ob- 
served in physiologic and pathologic conditions, are not thought to 
exert any toxic influence upon the body, it must be admitted that 
the observations were made upon animals, and that the results 
obtained may not be directly applicable to the human being. While 
a single large dose may not produce symptoms, it is not to be inferred 
that a continuous intoxication with the products of intestinal putre- 
faction may not lead to decided pathologic results. 



HO CLINICAL DIAGNOSIS. 

The Amount of Free HC1. 

Pure gastric juice, according to Ewald, Szabo. and Boas, contains 
from 2 to 3 p. m. of free HCI. 

In the digesting organ such amounts are met with at the height of 
digestion only after all albuminous and basic affinities have been 
saturated. The time at which free HCI can be demonstrated in the 
gastric contents after the ingestion of a meal will, hence, vary with 
the character of the food and its amount. "When but little work is 
to be accomplished, free HCI is found much sooner than otherwise. 
After Ewald's test-breakfast, for example, free HCI appears after 
thirty-five minutes, the point of maximum acidity being reached after 
from fifty to sixty minutes, corresponding to the presence of 1.7 p.m. 
Following Riegel's meal, on the other hand, free HCI appears after 
135 minutes and reaches its highest point, corresponding to 2.7 p.m.. 
in from 180 to 210 minutes. 

Clinically it is necessary to distinguish between euchlorhydry, or 
the secretion of a normal amount of free HCI (0.1 to 0.2 per cent,), 
hypochlorhydry, or the secretion of a deficient amount of free HCI 
(less than 0.1 per cent, i, hyperehlorhydry. in which more than 0.2 
per cent, is found, and, finally, anachlorhydry, in which no HCI at 
all is secreted. 

Euchlorhydry. Euchlorhydry, when associated with clinical 
symptoms pointing to gastric derangement, is most commonly ob- 
served in nervous dyspepsia. A chronic gastritis can always be 
excluded in the presence of a normal amount of free HCI, thus con- 
stituting a most important point in the differential diagnosis between 
these two conditions, which can but rarely be definitely made from 
the clinical symptoms alone. A normal secretion of free HCI is, 
furthermore, observed in some cases of atony or hypatonv of the 
muscular walls of the stomach. 

Hypochlorhydry. Hypochlorhydry is associated with all those 
diseases in which the secretory elements have been more or less 
damaged, as in subacute and chronic gastritis, some cases of ulcer of 
the stomach or the duodenum, in incipient carcinoma, dilatation, and 
atony. 

Anachlorhydry. Xot many years ago it was thought that the 
absence of free HCI from the gastric contents was pathognomonic of 
carcinoma of the stomach. This view, however, was soon aban- 
doned, as it was showu that cases of carcinoma occur in which HCI 



THE GASTRIC JUICE AJND OASTEIC CONTENTS. HI 

is not only present, but present in excessive amounts. This is true 
especially of those cases in which the malignant growth haa started 
upon the base of an old ulcer. It was, furthermore, shown that ana- 
ehlorhydry exists in almost all cases oi advanced chronic gastritis, 
and is a very common occurrence in neurasthenic and hysterical 
individuals, constituting the so-called hysterical anacidity. 

Hyperchlorhydry. The existence of hyperchlorhydry is gener- 
ally indicative of a gastric neurosis, aud is thus frequently met with 
in its simplest form in certain neurasthenic individuals. Associated 
with a continuous hypersecretion of gastric juice it constitutes the 
neurosis that has been described under the term hypersecretio acida 
et continua. Hyperchlorhydry is also of frequent occurrence in cases 
of gastric ulcer, and may even occur in carcinoma, notably in those 
cases in which, as has been stated above, the new growth has started 
from an old ulcer. 

Test for Free Acids. 

Following a physical examination of the gastric contents, and, if 
acid, a determination of the general acidity, the next step will be to 
determine whether or not the acid reaction is referable to the pres- 
ence of a free acid, of combined acids, or of acid salts. 

The Congo-red Test. Congo-red is a carmine-colored powder, 
while its solutions are of a peach- or brownish-red color, which 
changes to azure-blue upon the addition of a free acid, but re- 
mains unaffected in the presence of an acid salt. Congo-red may 
be employed in solution or in the form of a test-paper, which latter, 
however, is less delicate than the former, indicating the presence of 
0.01 per cent, of HC1, while a positive reaction can still be obtained 
with the aqueous solution in the presence of 0.0009 per cent, of free 
HC1. The solution to be employed should be moderately dilute, 
and the test-paper prepared by soaking in this solution filter-paper, 
free from ash, drying and cutting into suitable strips. In order 
to test for the presence of a free acid it is only necessary to immerse a 
strip of the test-paper in the filtered gastric juice, or to add a drop or 
two of the solution to a small amount of the juice, when in the pres- 
ence of free acid a blue color will develop which varies from a sky- 
blue to a deep azure, according to the amount present. 

A negative result will at once exclude the possibility of peptic 
activity, as pepsin acts only in acid solutious. 

If, however, the result of the test be positive, the nature of the 



112 CLERICAL DIAGNOSIS. 

free acid must still be ascertained, and it is. therefore, necessary to 
test for free HC1. for lactic acid, and for certain fatty acids. 

Tests for Free Hydro chloric Acid, 

The various reagents which may be employed are given below. 
arranged according to their degree of delicacy viz. : 

1. Dimethyl-amido-azj-benzjl .... 0.02 p.m. 

2. PMoroglucin-vanillin 0.05 

3. Eesorcin 0.05 

4. Methyl-violet 0.2 

5. Tropa?ohn 00 0.3 

6. Emerald-green 0.4 

7. AIohr*s reagent 1.0 

The Dirnethyl-amido-azo-benzol Test. This test has recently 
been introduced by Topfer. and to judge from his observations, as 
well as from the author's experience, is destined soon to replace the 
phlorogluoin-vanillin and resorcin tests in the clinical laboratory, for 
the reason that less time is required in its manipulation. The re- 
agent, moreover, may be employed in the direct estimation of the 
amount of free HO present The delicacy of the reagent is such 
that the neutral yellow color of the indicator is changed to a reddish 
tinge upon the addition of but one drop of a one-tenth normal solu- 
tion of HC1 in 5 c.c. of distilled water. Organic acids yield a red 
color only when present in amounts exceeding 0.5 per cent.: the 
presence of such quantities of albumin, peptones, and mucin, fur- 
thermore, as occur in the gastric contents will cause a negative 
reaction, even if organic acids be present to an amount far exceed- 
ing 0.5 per cent. Loosely combined HC1 and acid salts do not pro- 
duce this change in color. Its superior delicacy, as compared with 
the phioroglucin-vanillin and resorcin tests, is apparent from the 
fact that 5 c.c. of a 0.5 per cent, solution of egg-albumin, to which 
six drops of a one-tenth normal solution of HO have been added, 
still give a positive reaction with dimethyl-amido-azobenzol, while 
the phioroglucin-vanillin and resorcin reactions are negative. 

Tor practical parposes a 0.5 per cent, alcoholic solution is employed. 
One or two drops of this aie added to a trace of the gastric con- 
tents which need not be filtered : in the presence of free HO a beau- 
tiful cherry-red color develops, which varies in int^nsitv according 
to the amount of free HO present. A test-paper, prepared by 
soaking strips oi filter-paper, free from ash. in the 0.5 per cent, solu- 






THE GASTRIC J rid-: AND GASTRIC CONTENTS. 113 



tion and allowing them to dry, may also be employed. With gastric 
juice containing no Free HC1, as with distilled water, a yellow color 
results, the fluid at the same time becoming cloudy and beautifully 
fluorescent. 

The quantitative estimation of the free HC1 according to Topfer's 
method will be dealt with later on (see p. 117). 

The Phloroglucin-vanillin Test. The solution employed con- 
tains 2 grammes oi' phloroglucin and 1 gramme of vanillin, dis- 
solved in 30 c.c. of absolute alcohol : a yellow color results which 
gradually turns a dark golden-rea, changing to brown when ex- 
posed to light. The solution should, therefore, be kept in a 
dark-colored bottle. Lenhartz suggests using separate solutions of 
phloroglucin and vanillin, one or two drops of each being em- 
ployed in the test. Boas recommends a solution of ihe phloro- 
glucin and vanillin in the proportions indicated in 100 grammes of 
80 per cent, alcohol as still more sensitive and more stable. If a 
few drops of gastric juice, or even of the unfiltered gastric contents, 
containing 0.05 or more per cent, of free HC1, be treated with the 
same number of drops of the reagent, no change in color results, 
while upon the application of gentle heat — boiling and rapid evap- 
oration are to be avoided — a rose tint or exceedingly fine rose-colored 
lines develop at the edge of the drop, the occurrence of which is 
characteristic of the presence of free HC1. 

For practical purposes it is best to carry on this slow evaporation 
upon a thin porcelain butter-dish, the porcelain cover of a crucible, 
or in a small evaporating-dish of the same material. The color 
obtained in the presence of free HC1 is a rose color in every case, 
varying in intensity with the amount of acid present. A brown, 
brownish-yellow, or brownish-red color always indicates that ex- 
cessive heat has been applied, or that free HC1 is absent. 

Organic acids never produce this reaction ; it is not interfered with 
by their presence, or by albumins, peptones, or acid salts, which 
may occur in the gastric contents. 

A phloroglucin-vanillin test-paper, prepared by soaking strips of 
filter-paper, free from ash, in the solution and drying them, may 
also be employed. If a strip of this be moistened with a drop of 
gastric juice and gently heated in a porcelain dish, as already 
described, the rose-red color will be seen to develop in the pres- 
ence of free HC1, and does not disappear upon the addition of 
ether. 



114 CLINICAL DIAGNOSIS. 

The Resorcin Test. The solution consists of 5 grammes of re- 
sublimed resorcin and 3 grammes of cane-sugar dissolved in 100 
grammes of 94 per cent, alcohol. It is of equal delicacy as the 
pbloroglucin- vanillin solution and has, besides, the advantage of 
greater stability. 

Five or six drops of gastric juice are treated with three to five 
drops of the reagent and slowly evaporated to complete dryness 
over a small flame, when a beautiful rose- or vermilion-red mirror 
will be obtained, which gradually fades on cooling. If the reagent 
be employed in the form of a test-paper, a violet color at first 
develops, which upon the application of heat turns brick- red and 
does not disappear upon the addition of ether. 

The presence of acid salts, organic acids, albumins, or peptones 
does not interfere with the reaction. 

The methyl-violet and emerald-green tests cannot be recom- 
mended, as they are uncertain and may lead to error. 

The Tropseolin Test. Tropseolin 00, when employed according 
to the method given by Boas, is a very reliable reagent, indicat- 
ing the presence of 0.2 to 0.3 per cent of free HC1. Three or four 
drops of a saturated alcoholic solution of tropaeolin 00, which has a 
brownish-yellow color, are placed in a small porcelain dish or cover 
and allowed to spread over the surface. A like amount of gastric 
juice is then added and likewise allowed to flow over the surface of 
the dish ; upon the application of gentle heat beautiful lilac or blue 
stripes appear, which are said to be absolutely characteristic of free 
HC1. 

A tropaeolin test-paper may also be prepared by soaking filter- 
paper, free from ash, in the alcoholic solution for some time, and 
then drying and cutting it into strips. A few drops of gastric 
juice containing free HO produce a more or less pronounced brown 
color upon this paper, which turns lilac or blue upon the applica- 
tion of gentle heat. Organic acids, when present in large amouuts, 
likewise produce a brown color, which disappears, however, upon 
the application of heat, while a lilac or blue color never results. 

For ordinary purposes this test is sufficient, and recourse need 
only be had to the more delicate reagents when a negative or a 
doubtful result is obtained. 

Mohr's Test, as Modified by Ewald. Two c.c. of a 10 per 
cent, solution of potassium sulphocyanide are treated witn 0.5 c.c. 






THE GASTRIC JUICE AND GASTRIC CONTENTS. 115 



of a neutral solution of ferric acetate and diluted to 10 c.c. with dis- 
tilled water, a ruby-red colored solution resulting. Of this a few 
drops are placed in a porcelain dish, and a drop or two of the filtered 
gastric contents allowed to come slowly into contact with the re- 
agent. In the presence of free HC1 a light violet color develops at 
the point of contact between the two fluids, which turns a deep 
mahogany-brown upon mixing. 

The test is not interfered with by the presence of acid salts or 
peptones, but is not sensitive enough for practical purposes. 

The Benzopurpurin Test. Benzopurpurin 6B has been highly 
recommended by von Jaksch as a very sensitive test for HC1. It is 
best used in the form of a test-paper, prepared by soaking strips of 
filter-paper, free from mineral ash, in a concentrated watery solution 
of the reagent and allowing them to dry. 

In the presence of more than 0.4 gramme of HC1 in 100 c.c. of 
gastric juice the dark-red color of the test-paper immediately turns 
a deep blackish-blue. Should a brownish-black color develop, it is 
likely due to the presence of organic acids, or a mixture of these 
aud HC1. If the color be caused by organic acids only, it will 
disappear upon washing the strip with a little neutral ether, and 
the original color of the test-paper be restored ; but if due to a 
mixture of the two, the reaction is less marked, and does not dis- 
appear. According to Hellstrom, 0.39 milligramme of HC1 dis- 
solved in 6 c.c. of water can be recognized by the addition of only 
5 milligrammes of benzopurpurin. 

Acid salts, peptones, and serum-albumin do not seriously interfere 
with the reaction. 

Benzopurpurin test-paper von Jaksch claims to be more sensitive 
than the Congo-red paper. 

The Combined Hydrochloric Acid. 

It has been stated (see p. 104) that the determination of the 
total acidity of the gastric juice can only be referred to HC1 when 
organic acids and salts are absent. At the same time the free 
acid is titrated together with the loosely combined. The presence 
of free hydrochloric acid in normal amounts implies, of course, the 
existence of peptic activity, and indicates that all albuminous affini- 
ties have been saturated. From a practical standpoint, however, in 
the absence of free HC1 it is most important to know whether or 



116 



CL IXK A L LI A GNOSIS. 



not hydrochloric acid is secreted: L e., whether peptic digestion is 
at a standstill, or whether an amount is secreted that is only suffi- 
cient to saturate certain albuminous affinities without appearing in 
the free state. In the treatment of the various forms of gastric dis- 
ease, more especially those associated with an absence of free HC1, 
accurate knowledge in this respect is important. If no hydro- 
chloric acid at all is secreted, the stomach can be regarded only as 
a storehouse, as it were, and proteids must be ordered in such form 
that they may be subjected to the process of pancreatic digestion with 
as little delay as possible, the nutrition of the body being aided, 
if necessary, by a suitable administration of predigested food. If, 
on the other hand, an amount of hydrochloric acid is secreted suffi- 
cient to saturate the albuminous affinities of an ordinary meal, or at 
least of moderate amounts of proteids. the dietetic directions need 
not be so stringent. AVhile in the former case the absence of loosely 
combined hydrochloric acid usually indicates complete destruction of 
the glandular elements of the stomach — in other words, an irrepara- 
ble condition — a fair prognosis may be given when the amount of 
acid secreted is sufficient for the saturation of the albuminous 
affinities of an ordinary meal. The following table 1 shows the 
amount of HC1 necessary to saturate the affinities of known amounts 
of various articles of diet, the figures given referring to 100 c.c. or 
100 grammes : 



Milk. 


. 0.32-0.42 


gramme of pure 


HC1 


Beef (boiled) . 


. 2.0 


grammes 


'* 




Mutton (boiled) 


. 1.9 


a 


" 


tt 


Veal (boiled) . 


. 2.2 


u 


it 


tt 


Pork (boiled) . 


. 1.6 


" 


(i 


a 


Sweetbread (boiled) . 


. 0.9 


gramme 


■ i 


k 


Calves' brain (boiled) 


. 0.65 


tt 


ii 


" 


Ham (raw) 


. 1.9 


grammes 


tt 


tt 


Ham (boiled) . 


. 1.8 


u 


tt 


it 


Liver sausage . 


. 0.8 


gramme 


rt 


u 


Cervelat sausage 


. 1.1 


grammes 


it 


it 


Mettwurst 


. 1.0 


gramme 


It 


it 


Blood sausage . 


. 0.3 


<: 


a 


tt 


Graham bread . 


. 0.3 


(i 


tt 


a 


Pumpernickel . 


. 0.7 


,( 


u 


it 


Wheat bread 


. 0.3 


" 


" 


a 


Eye bread 


. 0.5 


(i 


tt 


<< 



1 Taken from Ehrlich : Dissert. Erlansren. 1893. 






THE GASTRIC JUICE AND GASTRIC CONTENTS 117 

Swiss cheese 2.6 grammes of pure HC1. 

Fromage de Brie . . . .1.3 " " " 

Edam cheese 1.4 " 

Roquefort cheese .... 2.1 " ,; " 

Beer (German) .... 0.07-0.15 gramme " " 

The Quantitative Estimation of the Hydrochloric Acid of 
the Gastric Juice. 

Topfer's Method. The free and combined HC1 is most con- 
veniently estimated according to Topfer's method, which is both 
simple and sufficiently accurate for clinical purposes. 

In this method the total acidity (a) of a given amount of gastric 
juice — i.e.. the acidity referable to the presence of free HC1, combined 
HC1, and acid salts — is first determined (lactic acid and the fatty 
acid-, if present, need not be removed), using phenolphthalein as 
an indicator. This is followed dv a determination of the acidity 
referable to free acids and acid salts in the same amount of gastric 
juice (6), using alizarin (alizarin monosulphonate of sodium) as an 
indicator. As this does not react with loosely combined HC1, the 
difference between " a " and " b" will indicate the amount of the 
latter. The free HC1 is finally estimated with dimethyl-amido-azo- 
benzol as an indicator (c), the difference between a and b -j- c giving 
the acidity referable to organic acids and acid salts. 

The solutions required are the following : 

1. A decinormat solution of NaOH. 

2. A 1 per cent, alcoholic solution of phenolphthalein. 
•'). A 1 per cent, aqueous solution of alizarin. 

4. A 0.5 per cent, alcoholic solution of dimethyl-amido-azo- 
benzol. 

Three separate portions of 5 or 10 c.c. of filtered gastric juice are 
measured off into three small beakers or porcelain dishes. To the 
first portion one or two drops of phenolphthalein are added, when it 
is titrated with the one-tenth normal solution of XaOH. It is neces- 
sary, however, to titrate to the point of a deep red, and not to the 
rose hue which first appears. It will be seen that upon the addi- 
tion of the first few drops of the one-tenth normal solution of NaOH 
the red color, which first appears, disappears on shaking. Upon 
further addition a point is finally reached when this no longer 
occurs, and the color of the entire solution suddenly turns to a rose. 
This rose color, however, is not the end-reaction that is to be ob- 
tained. If the titration is continued, it will be observed that a dark- 



118 CLINICAL DIAGNOSIS. 

red cloud forms in the light rose-colored solution, which disappears 
on shaking ; finally a point is reached when an additional drop no 
longer intensifies the color of the solution. This point is the end- 
reaction which must be reached. 

To the second portion three or four drops of the alizarin solution 
are added, when it also is titrated with the one-tenth normal solution 
until a pure violet color is reached. As some little practice is re- 
quired in order to determine accurately this point, Topfer advises to 
make previously the following simple tests : 

1. To 5 c.c. of distilled water add 2 or 3 drops of the alizarin 
solution, when a yellow color will result. 

2. To 5 c.c. of a 1 per cent, solution of disodium phosphate add 
the same number of drops, when a red or slightly violet color will be 
obtained. 

3. Five c.c. of a 1 per cent, solution of sodium carbonate treated 
with 2 or 3 drops of the alizarin solution will strike a pure violet, 
this being the color to be reached in the titration. 

In the third portion of the gastric juice the free HC1 is titrated, 
after the addition of 3 or 4 drops of the dimethyl-amido-azoben- 
zol, until the last trace of red — in the presence of free HC1 — has 
disappeared. A yellow color resulting upon the addition of the 
indicator demonstrates the absence of free HC1, as has been shown 
on page 113. The results are then calculated as shown in the follow- 
ing example : 

Ten c.c. of gastric juice, using phenolphthalein as an indicator, 
required 10 c.c. of the one-tenth normal solution in order to bring 
about the end-reaction, while a like amount titrated in the same 
manner with alizarin required 7 c.c. in order to bring about the same 
result. The difference between 10 and 7 — i. e., 3 — would thus indi- 
cate the number of c.c. necessary to neutralize completely the amount 
of hydrochloric acid in combination with albuminous material. As 
1 c.c. of the one-tenth normal solution represents 0.00365 gramme of 
HC1, the amount of the acid thus held will be equivalent to 0.00365 
X 3 == 0.01095 gramme of HC1 ; i. e., 0.1095 per cent. 

In the estimation of the free HC1 3.2 c.c. of the one-tenth normal 
solution were required, using dimethyl-amido-azobenzol as an indi- 
cator, corresponding to 0.00365 X 3.2; i. e., 0.1168 per cent., of HC1. 
The value of the total acidity in terms of HC1 is 10 X 0.00365 = 
0.0365 gramme for every 10 c.c. of gastric juice, or 0.365 per 
cent. 



THE GASTRIC JUICE AND GASTRIC CONTENTS \\\\ 

By deducting the amount of the free and combined 1IC1, viz., 
0.1095 0.1168 = 0.2263, from this, it is found thai the acidity of 
tlu 1 gastric juice referable to organic acids and acid salts amount- to 
0.1387 per cent., so that the results can be tabulated a^ Follow- : 

Free HC1 0.1168 per cent. 

Combined BC1 0.1095 

Organic acids and acid salts .... 13S7 " 



Total acidity .... 0.3650 per cent. 

The Method of Martius and Luttke (modified). This method 
is equally exact, but requires a greater expenditure of time. 

It is based upou the fact that upon incineration of the gastric juice 
the free HC1 and that loosely combined with albuminous material 
escapes, while the CI in combination with inorganic bases remains in 
the mineral ash, unless a very intense heat is applied for some time. 
By subtracting the amount of CI present in the latter form from 
the total amount, the quantity in combination with albuminous mate- 
rial and that occurring as free acid will be found. The total 
acidity of the gastric juice is then determined, and that referable 
to the presence of the free and combined HC1 subtracted there- 
from, the difference giving the amount of organic acids present. 
By determining the acidity due to the presence of free HC1 ac- 
cording to Topfer's method, aud deducting the amount found from 
that referable to the presence of free aud combined HC1, the amount 
of the latter is obtained. 

Reagents required : 

1. A solution of nitrate of silver iu nitric acid of such a strength 
that 1 c.c. shall represent 0.00365 gramme of HC1. 

2. Liquor ferri sulphur, oxydati. 

3. A decinormal solution of ammonium sulphocyanide. 

4. A one-tenth normal solution of XaOH. 

5. A 1 per cent, alcoholic solution of phenol phthalein. 

6. A 0.5 per cent, alcoholic solution of dimethyl-amido-azo- 
benzol. 

Preparation of the solutions : 

1. The silver nitrate solution : As a solution is required of such 
a strength that 1 c.c. shall be equivalent to 0.00365 gramme of 
HC1, the amount of silver nitrate that must be dissolved in 1000 c.c. 
of water is ascertained in the following manner : Since 169.66 (molec- 
ular weight of AgN0 3 ) parts by weight of AgXO, combine with 36.5 



120 CLINICAL DIAGNOSIS. 

parts of HC1 (molecular weight of HO), the amount of AgX0 3 
required for each c.c. is found from the equation : 

169.66 : 36.5 : : x : 0. 00365; 36. 5x = 0.6192590; x = 0.0169. 

In one c.c. of the silver nitrate solution 0.0169 gramme of AgN0 3 
must thus be present, or 16.9 grammes in the litre. This quantity, 
or roughly 17 grammes, is weighed off and dissolved in 900 c.c. of 
a 25 per cent/solution of nitric acid ; as the acid must be present 
in excess, the solution is purposely made too strong. To this solu- 
tion 50 c.c. of the liquor ferri sulphurati oxydati are added. The 
solution is then brought to the proper strength by titrating a known 
number of c.c. of a one tenth normal solution of HO with the same 
and correcting as usual. 

2. The ammonium sulphocyanide solution : A normal solution of 
ammonium sulphocyanide contains 75.98 grammes (molecular weight) 
per litre, and a decinormal solution 7.598 grammes. This quantity, 
or roughly 8 grammes, is dissolved in about 900 c.c. of water and 
the solution brought to the proper strength by titrating a known 
number of c.c. of the AgNO a solution with it, when every c.c. 
should correspond to 1 c.c. of the .AgX0 3 solution ; i. e., to 0.00365 
gramme of HC1. 

Method : 

1. To determine the total amount of CI present : 10 c.c. of filtered 
gastric juice — Martins and Livttke make use of the unfiltered gastric 
contents — are measured off into a small flask bearing a 100 c.c. 
mark, and treated with an excess of the one-tenth normal solution 
of AgNO s . Experience has shown that 20 c.c. are sufficient. The 
mixture is agitated and allowed to stand for ten minutes. Distilled 
water is then added to the 100 c.c. mark, the mixture agitated 
once more and filtered through a dry filter into a dry beaker. 
Fifty c.c. of the filtrate are then titrated with the one-tenth normal 
solution of ammonium sulphocyanide until the blood-red color which 
appears upon the addition of every drop — due to the formation of 
ferric sulphocyanide — no longer disappears on stirring. By mul- 
tiplying the number of c.c. of the ammonium sulphocyanide solu- 
tion used by 2 (the number of c.c. that would have been neces- 
sary for the precipitation of the excess of silver in 100 c.c.) and 
deducting the result from the number of c.c. of the one-tenth normal 
solution of AgN0 3 employed, viz., 20, the number of c.c. of the 
latter solution is found which was necessary to precipitate the CI 




THE GASTRIC JUIi E AND GASTRIC CONTENTS. 121 

contained in 10 c.c. of t ho gastric juice. As 1 c.c. of this solution 
represents 0.003G"> gramme of EG, it is only necessary to multiply 
this figure by the number of c.c, used in the precipitation of the CI. 

The resulting value, " T," expresses the total amount of CI present. 

As a general rule, it is not necessary to decolorize the gastric juice. 

IF let | u i red, however, 5 to 15 drops of a 5 per cent, solution of 

potassium permanganate maybe added to the 10 c.c. employed, after 

the mixture has stood for ten minutes. 

2. Determination of the amount of CI in combination with inor- 
ganic bases, u IV Ten c.c. of the filtered gastric juice are carefully 
evaporated to dryness in a platinum crucible over a water-bath, or 
upon a plate of asbestos (as the heat applied in the process of incin- 
eration is not very intense, a porcelain crucible may be employed), 
in order to avoid sputtering. The residue is then carefully, incin- 
erated over the open flame, the process being only carried to the 
point when the organic ash no longer burns with a luminous flame. 
Intense heat should be avoided, as the chlorides are volatilized upon 
the application of red heat. On cooling the ash is moistened with a 
few drops of distilled water and mixed with a stirring-rod, when 
the residue is extracted in separate portions with 100 c.c. of hot dis- 
tilled water, and filtered. This amount is usually sufficient to dis- 
solve out the chlorides present. If any doubt should exist, how- 
ever, it is only necessary to add a drop of AgN0 3 solution to a few 
drops of the last portion of the filtrate: the formation of a cloud, 
referable to silver chloride, will necessitate still further washing. 
The whole filtrate is then treated with 10 c.c. of the one- tenth nor- 
mal solution of AgX0 3 , and the amount of AgN0 3 consumed in the 
precipitatiou of the chlorides determined by titration with the one- 
tenth normal solution of ammonium sulphocyanide, as described 
above. The HC1 present in combination with inorganic bases is thus 
determined. The difference between the amount of HC1 present in 
combination with inorganic bases and the total amount of CI in 
terms of HC1 will then indicate the amounts of the free and of the 
combined HC1 present, termed " L" and " C," respectively ; hence 
T-F = LH-C. 

•3. The total acidity in terms of HC1 is further determined accord- 
ing to the method given elsewhere (see p. 104), and indicated by the 
letter "A." The difference between the total acidity and the amount 
of free and combined HC1 will represent the amount of organic 
acids and acid salts, " O"; hence O = A — (L + C). 



122 CLINICAL DIAGNOSIS. 

Finally the free HC1 may be determined according to the method 
of Topfer. The difference between the value thus found and that 
expressing the amount of free and combined HC1 will indicate the 
amount of the latter : hence (L -f- C) — L = C. 

Leo's Method. This method is based upon the observation 
that calcium carbonate combines with free and combined HO at 
ordinary temperatures to form neutral calcium chloride, while the 
acid phosphates are not affected. It is thus clear that by determin- 
ing the total acidity of the gastric juice, and deducting from this the 
acidity referable to acid salts, the amount of the physiologically 
active HC1 — i. e., of free and combined HO — is obtained. 

As it has been shown that in the presence of CaCL (formed. 
as indicated above, upon the addition of CaC0 5 ). owing to the for- 
mation of calcium monophosphate — CaHPO^. twice the quantity of 
XaOH is taken up by the same quantity of the diacid salt, it is 
necessary to titrate after the addition of an excess of CaCh. 

Reagents required : 

1. A one-tenth normal solution of XaOH. 

2. A 1 per cent, alcoholic solution of phenolphthalein. 

3. A concentrated solution of CaCh. 

-1. Chemically pure CaC0 3 . The purity of the salt may be tested 
bj stirring a small piece with water : the solution should not color 
red litmus-paper blue. A solution of the salt in dilute HO should 
not yield a precipitate when treated with H 2 SO.. 

Method : Oroarhc acids that may be present are first removed by 
shaking with ether, 50 to 100 c.c. of this being required for every 
10 c.c. of gastric juice. The total acidity of the gastric juice is then 
determined in 10 c.c. of the filtered liquid after the addition of 5 
c.c. of the concentrated solution of calcium chloride, the result being 
termed ••A."' 

The acidity referable to the presence of acid phosphates is deter- 
mined as follows : 15 c.c. of filtered gastric juice are treated with a 
point-of-a-knifeful of dry and chemically pure calcium carbonate, the 
mixture thoroughly stirred, aud passed at once through a dry filter. 
Ten c.c. of the filtrate, from which the C0 2 formed is expelled by 
means of a current of air, are then treated with 5 c.c. of the calcium 
chloride solution and titrated as above, the resulting value being 
termed " P." A — P is, hence, equivalent to L — C. The value 
of "C" can then be ascertained bv determining: the acidity referable 



THE GASTRIC JUICE AND GASTRIC CONTENTS 123 

to free HC1 according to Topfer'a method, and deducting the value 
found from L - C. 

This method is sufficiently accurate for practical purposes, and has 
the additional advantage of not requiring the expenditure of much 
time. 

The Ferments of the Gastric Juice and Their Zymogens. 

Pepsin and Pepsinogen. According to our present views, the 
zymogen of pepsin, viz., pepsinogen or propepsin, and not pepsin 
itself, is secreted by the chief cells of the fundus glands. This view 
is based upon the observation that an aqueous extract of the mucous 
membrane of the stomach of a fasting animal recently killed does 
not lose its digestive power when treated with a 1 per cent, solutiou 
of sodium carbonate at a temperature of from 38° to 40° C. for 
a considerable length of time, whereas pepsin itself is rapidly de- 
stroyed by very dilute solutions of the alkaline carbonates. It is 
thus natural to conclude that the glands of the stomach do not con- 
tain pepsin, but some other substance during the process of fasting 
which is capable of resisting the action of sodium carbonate, and 
which can be transformed into pepsin by the addition of HC1. This 
substance has been termed pepsinogen or propepsin. As a rule, jicpsin 
onlv is obtained from the mucous membrane of the digesting; organ, 
while at other times the physiologically inactive zymogen is found. 
As the zymogen, moreover, is probably always present together with 
pepsin in the gastric juice obtained from healthy individuals during 
the process of digestion, it is not clear whether the transformation of 
the zymogen into its ferment takes place in the body of the cell or 
after secretion. The greater part of the evidence so far is in favor 
of the latter view. 

This is not the place to enter into a detailed consideration of 
the various properties of pepsin, and it will suffice to say that the 
activity of the ferment is destroyed by even very dilute solutions 
of the alkaline carbonates. The same result is reached by exposing 
a watery solutiou of pepsin to a temperature of 70° C. , while in its 
dry state a temperature of 100° C. will not destroy its activity, as is 
shown by the fact that a specimen of pepsin thus treated is, on cool- 
ing, still capable of digesting albumins in the presence of HC1. 

While pepsin is capable of digesting albumins in the presence of 
other acids, viz., phosphoric, sulphuric, oxalic, acetic, lactic and 



124 CLINICAL D I AG X <J SIS. 

salicylic acid, stronger solutions of these must be present than in the 
case of HC1. TTitk lactic acid, for example, a satisfactory result is 
only reached with a concentration of from 12 to 18 grammes p.m., 
while of HC1 2 to 4 p.m. are sufficient. Larger or smaller amounts 
of the latter do not act so promptly. 

Very important from a practical standpoint is the fact that but 
small quantities of pepsiu are required to digest large amounts of 
albumin, and Petit, for example, claims that a pepsin preparation 
from his own laboratory was capable of dissolving 500,000 times 
its weight of fibrin in seven hours. This property on the part of 
pepsin of doing an amount of work that is entirely out of proportion 
to the amount of ferment present is common to all ferments, and is 
dependent upon the fact that the ferment itself undergoes no change 
during the process. 

Exact figures expressing the quantity of pepsin or of its zymogen 
produced in the twenty-four hours are lacking, hence only inferences 
can be drawn as to the physiologic activity of the same from the 
rapidity with which given amounts of albuminous material are 
digested. This, however, also depends to a large extent upon the 
nature and the concentration of the free acid present. In physio- 
logic conditions 25 c.c. of gastric juice will dissolve 0.05 to 0.06 
gramme of serum-albumin in one hour, the same amount of coag- 
ulated egg-albumin in three, hours, and a like amount of fibrin in 
one hour and a half. 

As abnormalities in the circulation and innervation of the stomach 
do not apparently influence the production of pepsin, or rather of its 
zymogen, a diminution in the degree of peptic activity, or its total 
absence, may be referred directly to disease of the stomach itself, viz., 
its glandular apparatus. The determination of the presence or 
absence and relative amount of pepsin in the gastric juice, hence, 
actually furnishes us with more directly useful information than the 
recognition of the presence or absence of free HC1, as the secretion 
of the latter is influenced by many factors which, as has been 
shown, only indirectly affect the process of digestion. 

As pepsin is formed from pepsinogen through the agency of a free 
acid, notably of HC1, its presence, in the absence of organic acids. 
in notable quantities at once indicates the presence of hydrochloric 
acid. It may be said, vice versa, that if free HC1 be present in the 
gastric juice, and the latter digest albumins, pepsin also will be 
found. Should the zymogen alone be present digestion will take 



THE GASTRIC JUH E AND GASTRIC CONTENTS. L25 

place only upon the addition of an acid, while an entire absence ol 
digestion upon the addition oi 1LC1 will indicate the absence of both 
pepsin and its zymogen. At times, though rarely, a "gastric 

juice" is met with which is capable of digesting albumin in the 
absence of SCI, owing to the presence of pancreatic juice — a 
point which may be of great value, both from a diagnostic and a 
prognostic point ol' view, indicating the existence of pancreatic 
digestion. 

In the differentia] diagnosis oi' a chronic gastritis and a neurosis, 
or a dyspeptic condition referable to hyperemia of the gastric mucous 
membrane, the demonstration of the presence of the zymogen in the 
absence of HC1 may, at times, be very important, bearing in mind 
the fact that circulatory and nervous disturbances do not apparently 
influence the production oi' pepsinogen. An entire absence of the 
latter would, of course, warrant the diagnosis of complete anadeny 
of the stomach. 

Tests for Pepsin and Pepsinogen. Test for the enzyme: If 
the presence of free HC1 has been previously ascertained, 25 c.c. of 
filtered gastric juice are set aside and kept at a temperature of from 
37° to 40° C. , a bit of coagulated egg-albumin, fibrin, or serum- 
albumin being added. In order to permit of a comparison of 
results the same amounts should always be taken ; 0.05 to 0.06 
gramme of egg-albumin, as has been shown, ought, then, to be 
digested after three hours under physiologic conditions. 

Test for the zj/moc/en : Should HC1 be absent the test is made in 
the same manner after the addition of from 3 to 5 drops of the offic- 
inal solution of HC1 to 25 c.c. of the filtrate. Under such condi- 
tions — i. e. } in the absence of free HC1 — pepsinogen alone, as a rule, 
is found. 

Quantitative Estimation. Unfortunately there is no method 
known by which the amount of pepsin or its zymogen can be accu- 
rately determined, relative values only being obtainable. 

Estimation of pepsin. To this end the method devised by Brlicke, 
as modified by Jaworski, is probably the best: 200 c.c. of a decinor- 
mal solution of HC1 are introduced into the fasting organ by means 
of the stomach-tube, and the contents removed after half an hour. 
These are filtered and brought to the strength of a one-twentieth 
normal solution of HC1, and then mixed with a one-twentieth normal 
solution of HC1 until all digestive power has disappeared. To this 
end one part of gastric juice is treated with nine times its volume of 



B 


u 


0.9 


C 


ll 


0.8 


D 


" 


0.7 


E 


ll 


0.6 


F 


ll 


0.5 


G 


n 


0.4 


H 


it 


0.3 


I 


" 


0.2 


K 


u 


0.1 


L 


n 


0.05 



126 CLINICAL DIAGNOSIS. 

a one-tenth normal solution of HC1 (i. e., 1 : 10). The following 
tabes are then prepared : 

A contains 1.0 cc. of gastric juice and 9.0 cc. T V normal HC1. 

u 91 ii 

ll tl ll q 9 ll ll ll 

ii ii ii q q ii n n 

ll ll <( Q I ll ll ll 

ll ll ll Q X .1 ll ll 

ii ii u Qfi " u ,c 

ll ll ll Q J ll l( tl 

ll 9i g ll 

ll It tl Q Q tl ll ll 

" 9.95 " 

To each tube a flake of fibrin is added. If it is now found that, 
of two given specimens, digestion ceases in tube F in the first, and 
in the second in tube K, the relation in the amount of pepsin between 
the two tubes is as 1 : 5. (Boas.) 

Estimation of pepsinogen. In order to estimate the amount of 
pepsinogen the method of Boas may conveniently be employed. To 
this end the gastric juice is diluted with distilled water in varying 
proportions, such as 1 : 5, 1 : 10, 1 : 20, etc. A known quantity of 
coagulated albumin is added to each specimen, as also one or two 
drops of an officinal solution of HC1 to every 10 cc. employed. 
These tubes are kept at a temperature of from 37° to 40° C, and 
the degree of dilution noted at which the bit of egg-albumin con- 
tinues to be dissolved. The greater the degree of dilution at which 
digestion still takes place, the greater the amount of pepsin or 
its zymogen present. 

The Milk- curdling Ferment and its Zymogen, viz., Chy- 
mosin and Chymosinog'en. A great deal of what has been said 
above regarding pepsin and its zymogen also holds good for chyrno- 
sin and its proenzyme. The latter thus also appears to be formed by 
the cell, as a neutral aqueous extract of the mucous membrane of the 
stomach does not, as a rule, contain the ferment, but the zymogen, 
the former only resulting from the latter upon the addition of a free 
acid. It differs from pepsin in that it can exert its physiologic 
activity in feebly acid, neutral, and even feebly alkaline solutions. 
Exposure of an active solution of chymosin containing 3 p.m. of 
free HC1, moreover, to a temperature of from 37° to 40° C, leads 
to its destruction, while pepsin is not affected under the same con- 
ditions. 






THE GASTRIC JUICE AND OASTRH CONTENTS 127 

[ts specific action is exerted upon milk or lime-containing solu- 
tions of casein, leading to a coagulation of the latter in neutral or 
feebly alkaline solutions. 

In this connection it is important to note that the addition of a 
few e.e. of a solution of CaCl 2 , or any other soluble lime salt, results 
in a transformation of the zymogen into the physiologically active 
ferment, and that HC1, while it normally causes such transformation, 
is not absolutely necessary in the presence of the former reagent. 

ruder physiologic conditions chymosin and its zymogen are always 
present in the gastric juice of man. In disease the inferences that 
can be drawn from a quantitative estimation of the ferment and its 
zymogen have been well formulated as follows, by Boas, to whom 
we are especially indebted for a great deal of valuable information 
in this connection: 

1. Notwithstanding the absence of free HC1, chymosin may still 
be present, although in minimal traces ; L e., demonstrable with a 
dilution of from 1 : 10 to 1 : 20 (see method given on p. 128). 

2. In the absence of free HC1 the zymogen may still be present 
in normal amouuts; i. e., with a dilution of from 1 : 100 to 1 : 150. 
The presence of the zymogen, especially when repeatedly observed, 
permits of the conclusion with a high degree of probability, and even 
with absolute certainty, that we are not dealing with an organic dis- 
ease of the stomach, but with a neurosis, or a hyperpemic condition 
of the mucous membraue referable to disease of other organs. 

3. The zymogen may occur in moderately diminished amount, 50 
per cent, only being present, usually owing to the existence of a gas- 
tritis which has not as yet reached its highest degree of severity. The 
nearer the amount of zymogen approaches to normal, the greater will 
be the probability of an ultimate recovery under suitable treatment. 

4. The amount of the zymogen is greatly diminished (dilutions of 
1 : 10 to 1 : 25 yielding a negative result), or may be absent alto- 
gether. In cases of this kind a severe and usually incurable gas- 
tritis exists, either primary or occurring secondarily to carcinoma, 
amyloid degeneration, etc. 

5. In 1, 2, and 3 the re-establishment of the secretion of HC1 may 
be attempted with some prospect of success by means of stimulating 
remedies. 

These conclusions are based upon the employment of Ewald's t< st- 
breakfast, and cannot be applied to observations made after other 
test-meals, without previous studies in this direction. 



128 CLINICAL DIAGNOSIS. 

Testing for the presence of chymosin and its zymogen, moreover, 
is of decided value in cases in which alkaline material is vomited, and 
where we may be called upon to decide whether this contains con- 
stituents of the gastric juice or not. 

Tests for Chymosin and Chymo smog-en. Test for the enzyme: 
Five to ten c.c. of milk are treated with from three to five drops of 
the filtered gastric juice and kept at a temperature of from 37° to 
40° C. for ten to fifteen minutes. If coagulation occurs during 
this time, it may be definitely concluded that the enzyme is present. 

Test for the zymogen: 10 c.c. of filtered and feebly alkaline gas- 
tric juice are treated with 2 or 3 c.c. of a 1 per cent, solution of CaCl 2 , 
and kept at a temperature of from 37° to 40° C, when the formation 
of a thick cake of casein will be observed within a few minutes in 
the presence of the zymogen. 

Quantitative Estimation. Of the enzyme : This is based upon 
the fact that upon gradually diluting a specimen of gastric juice a 
point is finally reached at which a chymosin reaction can no longer 
be obtained, the value being, of course, a relative one. Under phy- 
siologic conditions a positive reaction can still be obtained with a 
degree of dilution varying between 1 : 30 and 1 : 40. 

The gastric juice is neutralized with a very dilute solution of 
NaOH and tubes prepared containing from 5 to 10 c.c. of the gastric 
juice, variously diluted in the proportion of 1 : 10, 1 : 20, 1 : 30, etc., 
to which an equal amount of neutral or amphoteric milk is added. 
The tubes, properly labelled, are kept at a temperature of from 37° 
to 40° C. , and the degree of dilution noted at which coagulation still 
occurs. 

Of the zymogen: The gastric juice is rendered feebly alkaline and 
tubes are prepared containing equal amounts of milk and gastric 
juice, the latter variously diluted as above directed ; the examination 
is then carried on in the same manner. Normally a positive reaction 
is obtained with a dilution varying between 1 : 100 and 1 : 150. 
Allowance must, of course, be made for the error incurred in 
diluting the gastric juice during the process of neutralization. 

The Products of Gastric Digestion. 

The Digestion of Native Albumins. The first step in the pro- 
cess of albuminous digestion in the stomach is one of swelling, which 
may be readily observed when a flake of fibrin, for example, is 
placed in gastric juice, and the temperature of the latter maintained 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 129 

between 37° and 40° C. Very soon simple dissolution takes place, 
which is followed by the process of " denaturization," asNeumeister 

terms it, in which the native albumins are transformed into acid albu- 
mins or syntonins, owing to the continued activity of the IIC1 and 
pepsin. The pepsin, however, only acts as an adjuvant to the acid, 
and I1C1 alone is capable of effecting the same result. While in the 
absence of pepsin more concentrated solutions of the acid and a higher 
temperature arc required, the temperature of the body and the amount 
of HC1 secreted by the stomach are sufficient when pepsin is present. 
The latter in the absence of free HC1 is perfectly inert. 

The " denaturization " of the native albumins is followed by a 
splitting up of the albuminous molecule and a process of hydra- 
tion, the so-called primary albumoses, of which there are two, viz., 
protoalbumose and heteroalbumose, being the first products thus 
formed. 

Dysalbumose, it may be stated in passing, is merely a modified 
form of heteroalbumose, which results from the latter when this is 
dried or kept under water for some time. 

During the further process of digestion a deuteroalbumose results 
from each of the primary albumoses, and from these finally peptones, 
to which, in contradistinction to the peptones formed during the pro- 
cess of pancreatic digestion, the term " amphopeptone " has been 
applied by Kuhne. 

The relation existing between the various products of gastric 
digestion may be seen from the table below (taken from Neu- 
meister) : 

Native albumin. 



I I 

Protoalbumose. Heteroalbumose (dysalbumose). 

I I 

Deuteroalbumose. Deuteroalbumose. 

I I 

Peptone (amphopeptone). Peptone (amphopeptone.) 

The transformation of native albumins into peptones, as described, 
was first worked out for fibrin, but was subsequently shown to hold 
good for all native albumins of both vegetable and animal origin. 
Chittenden proposes the generic term " proteoses " for these various 
products of digestion, in contradistinction to those resulting from 
albuminoids. Yitellin thus first yields two primary vitelloses, viz., 
a proto- and a heterovitellose, which are transformed into deutero- 
vitelloses and finally into peptones. The albumoses of fibrin are 

9 



130 CLINICAL DIAGNOSIS. 

similarly termed fibrinoses ; those of the globulins, globulinoses ; and 
those of myosin, myosinoses. 

The digestion of casein, which belongs to the class of nucleoalbu- 
mins, differs from the process described. The casein of the milk is 
present in solutiou as a neutral calcium salt, and as casein has the 
character of a polybasic acid, CaCl 2 the corresponding acid casein 
salt will result in the presence of the HC1 of the stomach ; still 
later, when more HC1 has been secreted, insoluble casein as such will 
be found. While HC1 is thus capable of causing the precipitation 
of casein, it has also been shown that the same result may be 
reached in the absence of HC1, and, according to Hammarsten, is 
brought about in consequence of a hydrolytic action on the part of 
the chymosin present, the Ca salt of paracasein (cheese) and a small 
amount of albumose-like posset-albumin being formed. This latter 
process is now supposed to take place in the stomach after the HC1 
has previously transformed the neutral into the acid casein salt. 
When this stage is reached the paracasein is split up into an albumin 
and an insoluble nuclein, owing to the action of HC1 and pepsin. 
The albumin is then further digested as described, two primary 
caseoses first resulting, which are then transformed into deutero- 
caseoses, and these fiually into peptones. 

The remaining proteids, such as haemoglobin, glucosides, etc., are 
similarly acted upon by the gastric juice, being first split up into the 
corresponding albumins and their pairlings. Haemoglobin is thus 
broken down into hsematin and an albumin, which latter undergoes 
the same process of digestion as seen in the case of the native 
albumins. 

The Digestion of the Albuminoids. Of the albuminoid bodies 
only collagen and elastin undergo digestion in the stomach, gelatoses 
and elastoses being formed during the process, while keratin passes 
off undigested. Heteroproteoses, however, are formed from neither 
collagen nor elastin, but merely protoproteoses, which in turn are 
transformed into deuteroproteoses, of which there is only one kind, 
viz., that corresponding to the protoproteose, peptone finally resulting. 

The Digestion of Carbohydrates. The secretion of the stomach 
itself is not capable of digesting carbohydrates. There appears to 
be no doubt, however, that a transformation of starches into sugar 
takes place during the earlier stages of digestion. This is owing to 
the continued action of the ptyalin of the saliva (see p. 87) in the 
stomach, which goes on until the amount of HC1 secreted reaches 






THE QASTRIt JUICE AND OASTRIi CONTENTS. 131 

0.01 or more percent., it being remembered that the transformation of 
Starches into sugar goes on best in a neutral or feebly alkaline medium. 

The question, whether or not a di astatic ferment occurs in the 
mucus secreted by the stomach itself is unimportant, as cases have 
but rarely been observed in which there was an absence of ptyalin 
from the saliva. 

As indicated in the chapter on Saliva, a large number of interme- 
diary products are formed in the transformation of starch into sugar, 
of which an idea may be had from the accompanying table : 

Starch. 

I 
Amidulin. 

I 



Erythrodextrin. Maltose. 

Achroodextrin a. Maltose. 

I I 

Achroodextrin ->. Maltose. 

Achroodextrin 7 (maltodextrin). Maltose. 

I I 

Maltose. Maltose. 

In the mouth this transformation is very rapidly effected in the 
case of certain starches, such as cornstarch and rye-starch, and it is 
possible to demonstrate the presence of sugar after from two to six 
minutes. Potato-starch, on the other hand, requires a much longer 
time, viz., from two to four hours. This difference is entirely 
dependent upon the varying degrees of resistance offered to the 
action of the saliva by the enclosing envelope of cellulose, as is 
apparent from the fact that a paste made from potatoes is just as 
rapidly digested as one made from rye. 

For practical purposes, the digestion of carbohydrates in the 
stomach may be disregarded as insignificant. 

Fats are not Digested at all in the Stomach. 

From the above considerations it is apparent that under physiologic 
conditions a mixture of these various products is met with in the 
stomach at the height of digestion, and it might be expected that 
from a preponderance of one over the other definite and valuable 
conclusions as to the digestive power of the organ could be reached. 
While this is true in a certain sense, the quantitative methods of 
analysis that would have to be employed in order to obtain defi- 



132 CLINICAL DIAGNOSIS. 

nite data are as yet too complicated for the purposes of the clinician, 
and from the simple qualitative tests not much information can be 
derived. The recognition of the presence of peptones would thus 
merely indicate the presence of HC1 and pepsin in a general way, 
as peptones may be formed in the absence of HC1 and in the 
presence of organic acids, which may be found in pathologic 
conditions. Moreover, a portion of the albumin of milk, eggs, 
meat, etc., is already peptonized, so to speak, during the process 
of boiling. It is not surprising that peptones may probably be 
demonstrated in every specimen of gastric contents. 

A large amount of syntonin and primary albumoses in the pres- 
ence of a feeble peptone-reaction must, of course, be regarded as ab- 
normal, pointing to a defective secretion of either HC1 or enzymes, 
or of both. The same may be said to hold good when a pronounced 
peptone-reaction disappears upon the removal of syntonin and the 
primary albumoses. 

As far as the examination for the products of carbohydrate diges- 
tion is concerned, it may be stated, as a general rule, that in the 
presence of a normal amount of HC1 erythrodextrin can usually 
be demonstrated near the end of gastric digestion, while achroodex- 
trin is almost always obtained at the same time in the absence of 
free HC1, so that the tests for the presence of these two bodies may 
be regarded as roughly indicating the presence or absence of free 
HC1, and as therefore yielding the same information as the tests for 
this. Boas draws attention to the fact, however, that ptyalin may, 
at times, though rarely, be absent, when conclusions drawn from 
these tests as to the presence of HC1 would be erroneous. 

Finally, the tests for sugar in the gastric juice do not furnish any 
information that is of practical value. 

Analysis of the Products of Albuminous Digestion. 

In order to separate the various bodies referred to from each other 
the following procedure is employed : 

The filtered gastric contents are carefully neutralized with a dilute 
solution of NaOH, using litmus-paper to determine the reaction, a 
small drop of the mixture being placed upon the paper from time to 
time during the addition of the NaOH, until no change in color is 
produced either on the red or the blue paper. If syntonin be pres- 
ent, it will be precipitated, and can be collected on a small filter. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 133 

Upon the addition of an excess of a dilute acid or an alkali this 
precipitate will again be dissolved. The filtrate is feebly acidified 
by the addition of a few drops of a very dilute solution of acetic 
acid, treated with an equal volume of a saturated solution of common 
salt, and brought to the boiling-point. Any native albumin that 
may be present in solutiou is thus coagulated and can be filtered 
off on cooling. In the filtrate the albumoses and peptones remain. 
The presence of the former may be demonstrated by adding a few 
drops of HX0 3 to a specimen, when a precipitate will form which 
dissolves upon the application of heat, to reappear on cooling ; if 
necessary, the specimen may be diluted. 

Should the deuteroalbumoses of vitellin or myosin be present, 
this test yields a negative result, and a precipitate only occurs when 
the solution, acidified with nitric or acetic acid, is completely saturated 
with NaCl. 

The presence of primary albumoses, on the other hand, may be 
established by adding pieces of rock-salt to the neutral solution, 
causing the formation of a precipitate in their presence. The albu- 
moses may be roughly separated from the peptones by saturating 
the acidified filtrate just obtained with pulverized ammonium 
sulphate, whereby the albumoses are almost entirely precipitated. 
A small portion of the deuteroalbumoses, however, resulting from 
the protoalbumoses remains in solution and passes into the filtrate, 
which also contains all of the amphopeptone. In the filtrate these 
products may be demonstrated by adding a concentrated solution 
of XaOH, care being taken to keep the temperature from rising 
too high by immersion in cold water, until all ammonium sulphate 
has been transformed into sodium sulphate and a slight excess of 
the XaOH is present. The sodium sulphate, which separates out 
during this process, is allowed to settle, and a 2 per cent, solution 
of sulphate of copper carefully added drop by drop to a specimen 
taken from the supernatant fluid. In the presence of peptones a 
rose to a purplish-red color will develop. 

The peptones may be obtained after careful neutralization of the 
filtrate, having first diluted this with an equal volume of distilled 
water, by the addition of a solution of tannic acid, care being taken 
to avoid an excess, as the peptone-precipitate is soluble under such 
conditions. 

From the following table an idea may be formed of the reactions 
of these various bodies : 



134 



CLINICAL DIAGNOSIS. 
Beaction of the Individual Proteids. 



Globulin. 


Syntonin. 


Hemialbumose. 


Peptone. 


Soluble in 


Dilute solutions of 
sodium chloride 
and of magnesium 
sulphate. 


Dilute acids and 
alkalies. 


Water, acids, alka- 
lies, and salts. 


Water, acids, acids 
+ salts, alkalies. 


Insoluble in 


Water. 


Water and neutral 
salt solutions. 






Precipitated by 


Much water, heat- 
ing to 75° C, satu- 
ration with mag- 
nesium sulphate 
from its solutions 
in neutral salts. 


Neutralization of its 
solutions in dilute 
acids, by means of 
sodium chloride or 
heating to 75° C. 
from acid solu- 
tions. 


Acetic acid-i-sodium 
chloride, concen- 
trated nitric acid, 
acetic acid, and 
potassium ferro- 
cyanide in the 
cold. 


Bichloride of mer- 
cury, tannic acid, 
iodo-mercuric io- 
dide of potassium, 
phospho - tungstic 
and phospho-mo- 
lybdic acids. 


Biuretic re- 
action 


Violet. 


Violet. 


Rose to purple. 


Rose to purple. 



Tests for the Products of Carbohydrate Digestion. 

Starch may be recognized by the fact that it strikes a blue color 
with a solution of iodo-potassic iodide, while the same solution gives 
a violet or mahogany-brown with erythrodextrin. To this end it is 
only necessary to add a drop or two of Lugol's solution to a few c.c. 
of the filtered gastric juice. The presence of achroodextrin may be 
inferred if no change in color is produced upon the addition of the 
reagent. 

Maltose and dextrose, which both react with Fehling's solution 
and undergo fermentation, differ from each other by the fact that the 
former does not reduce Barfoed's reagent, which is prepared by add- 
ing a 1 per cent, solution of acetic acid to a 0.5 to 4 per cent, solution 
of acetate of copper. Upon boiling a few c.c. of this solution, and 
adding a small amount of gastric juice, red cuprous oxide will be 
precipitated in the presence of maltose. 

Lactic Acid. 

Mode of Formation and Clinical Significance. It was for- 
merly thought that the acidity of the gastric juice was referable to 
the presence of lactic acid, as the latter can always be demonstrated 
in the beginning, at least, of the process of digestion, and the HC1 
was even thought to result from an action of the lactic acid upon the 
chlorides ingested. That this view was erroneous C. Schmidt suc- 
ceeded in demonstrating beyond a doubt, as has been shown on p. 102. 
An explanation of the presence of lactic acid suggested itself when 
Miller found that normally various bacteria occur in the mouth 
capable of forming lactic acid from sugar, and that a number of 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 135 

bacteria can be isolated from the gastric contents which are capable 
of causing an acid fermentation in sugar-containing media. 

There would, hence, be nothing surprising in the constant occur- 
rence of lactio acid, as the two principal factors necessary for its 
formation are probably always present after the ingestion of an ordi- 
nary meal, viz., carbohydrates and bacteria capable of causing lactic- 
acid fermentation. The absence of the lactic acid during the later 
stages of digestion was, furthermore, explained by the fact that 
lactic-acid fermentation ceases in the presence of from 0.7 to 1.6 pro 
mille of HC1 ; i.e., in the presence of the amount of HC1 which is 
found in normal gastric juice. The occurrence of lactic-acid fermen- 
tation in the stomach was, hence, until quite recently regarded as an 
established fact. At this stage Martius and Liittke, employing the 
method already described, found " that the accurately determined 
curve of acidity referable to HC1 coincided in all respects, even at 
the beginning of the process of digestion, with the curve referable 
to the total acidity," so that lactic acid as a physiologic constituent 
could not have been present in the gastric contents examined. 

Recent researches of Boas, moreover, appear to prove beyond 
a doubt that in physiologic conditions no appreciable amounts of 
lactic acid are formed during the process of digestion, and that 
the lactic acid found after an ordinary meal has been introduced 
into the stomach as such. That lactic acid is actually present in 
the various kinds of bread has been definitely proved, and it is, 
hence, not permissible to make use of any test-meal containing 
lactic acid when the question as to its formation in the stomach is 
to be considered. For these reasons Boas suggests the use of simple 
oatmeal-soup, to which salt only has been added, to be taken on an 
empty stomach. For practical purposes this is probably not always 
necessary, as the amount of lactic acid found after Ewald's test- 
breakfast may be disregarded in health, and an increased amount be 
directly referred to pathologic conditions. 

The fact that the lactic acid disappears, or at least is no longer 
demonstrable, at the height of digestion, Boas refers to resorption 
or a carrying off of the acid introduced on the one haud, or to an 
interference of the HC1 with the delicacy of the reagent usually 
employed — i. e., Uffelmann's reagent — on the other. Pathologically 
the same rule may be said to hold good, since Boas was unable to 
demonstrate its presence after the exhibition of his test-meal in 
various diseases of the stomach, viz., chronic gastritis, atony and 



136 CLINICAL DIAGNOSIS. 

dilatation referable to myasthenia, or pyloric stenosis following ulcer. 
Mere traces, which were occasionally observed, are of no significance, 
and possibly referable to lactic-acid fermentation having taken place 
in the mouth. In all of the cases examined, moreover, no organic 
acids could be demonstrated by the method of Hehner-Seemann 
(see p. 144). 

It is apparent then that notwithstanding stagnation of the gastric 
contents and the absence of free HC1 in normal amounts, lactic acid 
is not necessarily formed in the stomach, even in the presence of 
carbohydrates. In only one disease of the stomach was lactic acid 
found in notable quantities, viz., carcinoma, an observation which 
is in accord with the fact that Uffelmann's test here yields a marked 
reaction — i. e., a deep lemon or canary -yellow color — even upou the 
addition of but few drops of the gastric juice, while in the benign 
affections only a pale-yellow, brownish, or grayish color is obtained. 

Boas's test-meal should be given the evening before the examina- 
tion, the stomach having been previously washed free from all rem- 
nants of food, and the remaining contents examined the next morning. 

In an analysis of fourteen cases of carcinoma Boas was able to 
demonstrate the presence of lactic acid in amounts varying between 
1.22 and 3.82 p.m. in all cases but one. In this connection it 
may be mentioned that under physiologic conditions the amount of 
lactic acid obtainable after Ewald's test-breakfast varies between 
0.1 and 0.3 per cent. 

That stagnation of the gastric contents and the absence of free 
HC1 alone are not capable of causing the formation of lactic acid 
has been seen, and it is, hence, difficult to explain why in carcinoma 
only lactic-acid fermentation should occur. Whether the malignant 
growth itself must be regarded as one of the principal factors in this 
connection, as Boas suggests, must still remain an open question. 

If the difficulties that may be encountered in the diagnosis of 
carcinoma, and notably so in the beginning of the disease, be 
remembered, such observations must be regarded as of great im- 
portance, for, if confirmed, we should actually be in possession of a 
" specific " symptom of carcinoma of the stomach. A negative result, 
however, apparently does not exclude this diagnosis. The fact that 
lactic acid is present in the beginning of this disease makes Boas's 
observations still more important, as definite results from operative 
interference can only be expected during the earliest stages of the 
malady. 



THE GASTRIC JUICE AND GASTRIC CONTENTS, \:\7 

Owing to the interest which attaches to this subject, it may not be 
out of place to refer briefly to the following observation of Koch: 

In a case in which ulcer of the stomach existed, associated with the 
presence of free HC1, suddenly a positive HC1 reaction could no 
longer be obtained, while lactic acid appeared and increased steadily 
in amount from week to week. A tumor could not be demonstrated 
on physical examination. Soon after the patient died, and at the 
autopsy a carcinoma of the stomach was found upon the base of a 
pyloric ulcer. 

Chemically the formation of lactic acid from starch may be repre- 
sented by the following equations: 

I. 2C 6 H 10 O 5 + H 2 = C 12 H 22 O n (milk sugar). 
II. CVEUOn-f H.,0 = 2C 6 H 12 6 (glucose). 
III. 2C 6 H 12 6 = 4C 3 H 6 3 (lactic acid). 

It should, finally, be mentioned that only that form of lactic acid 
which results from fermentative processes is of interest in this 
connection, and not the sarcolactic acid contained in meat — a point 
which interferes with the general usefulness of Riegel's test-meal. 

Tests for Lactic Acid. For the reasons indicated Boas's test- 
meal (see p. 97) should be employed whenever it is desired to test for 
lactic acid in the gastric contents. If the case under examination 
shows well-marked symptoms of stagnation of the gastric contents, 
the stomach should be washed out completely in the evening, the soup 
given then, and the gastric contents procured the next morning, 
before any food or liquid is taken. Otherwise the test-meal may 
be given in the morning on an empty stomach, without previous 
lavage, and the contents examined one hour later. 

Uffelm ann's Test. Heretofore USelmann's reagent was quite 
constantly employed in testing for lactic acid, but everyone who 
has had occasion to make frequent use of this reagent in clinical 
work must have been struck with the unreliability of the results 
so often obtained. In a large majority of the cases thus exam- 
ined, particularly if Ewald's test- break fast is employed, a char- 
acteristic reaction — i. e., the occurrence of a lemon or canary-yellow 
color — is not seen, notwithstanding the presence of lactic acid, but a 
pale-yellow, brownish, grayish-white, or even gray color obtained 
instead, often leaving it doubtful whether lactic acid be present or 
not. Aside from doubtful results, the value of the test is greatly 
diminished by the facts that glucose, acid phosphates, butyric acid, 
and alcohol give the same reaction, aud that in the presence of 



138 CLINICAL DIAGNOSIS. 

such amounts of HC1 as are found at the height of normal digestion 
lactic acid is not indicated by the reagent. All these difficulties 
have long been appreciated, and in order to obviate at least some 
of them it was proposed to apply the test to an aqueous solution 
of the ethereal extract of the gastric contents: 

To this end 5 to 10 c.c. of the filtered gastric juice are extracted 
by shaking with from 50 to 100 c.c. of neutral sulphuric ether in a 
stoppered separating-fnnnel for about twenty to thirty minutes, and 
the ethereal extract evaporated over a water-bath, or the ether 
distilled off (no flame). The residue is then taken up with from 5 
to 10 c.c. of distilled water, and tested as follows: Three drops of 
a saturated aqueous solution of the sesquichloride of iron are mixed 
with three drops of a concentrated solution of pure carbolic acid 
and diluted with water until an amethyst-blue color is obtained. 
To this solution a portion of the ethereal extract is added, when in 
the presence of only 0.1 per cent, of lactic acid a lemon or canary- 
yellow color is obtained. 

Kelling's Method. Five to ten c.c. of gastric juice are diluted 
from ten to twenty times with water and treated with one or two 
drops of a 5 per cent, aqueous solution of the sesquichloride of iron. 
In the presence of lactic acid a distinct green color is obtained, if 
the tube be held to the light. This test is more reliable than that 
of Uffelmann, as a positive reaction is only obtained in the presence 
of lactic acid. 

Strauss's Method. Instead of evaporating the ether as in 
the above method, the ethereal extract may be directly examined by 



Strauss's apparatus for the approximative estimation of lactic acid. 

shaking with a freshly prepared solution of the sesquichloride of 
iron, as suggested by Fleischer. Making use of this principle Strauss 
has recently constructed an apparatus (Fig. 33) which may be found 
very convenient and which permits of roughly determining the amount 
of lactic acid present. The instrument is essentially a separating- 



THE GASTRIC JUICE AND GASTRIC CONTENTS. \:\\\ 

tunnel oi 30c.c. capacity, bearing two marks, oi which the one corre- 
sponds to 5 c.c, the other to 25 c.c. The apparatus is filled with 

gastric juice to the mark 5, when ether is added to the 25 0.C line. 
After shaking thoroughly the separated liquids are allowed to escape 
by opening the stopcock until the 5 c.c. mark is reached. Distilled 
water is then added to the 25 mark, and the mixture treated with 
two drops of the officinal tincture of the sesquichloride of iron, 
diluted in the proportion of 1 : 10. Upon shaking the water will 
assume an intensely green color, if more than 1 p.m. of lactic acid 
be present, while a pale green is obtained in the presence of from 
0.5 to 1 p.m. The tincture of iron should be kept in a dark-colored 
dropping-bottle of about 15 c.c. capacity. 

It will be observed that ouly large amounts of lactic acid, which 
are alone of importance from a diagnostic point of view, are indi- 
cated by the apparatus. Small amounts, as those introduced with 
Ewald's test-breakfast, or referable to lactic-acid fermentation in 
the mouth, are not indicated, so that confusion as to the presence 
or absence of the acid can never arise. 

Boas's Method. In doubtful cases the following method should 
be employed, as with it, following the exhibition of Boas's test- 
meal, all possible errors already referred to can be avoided. 

Principle of the method : When a solution of lactic acid is treated 
with a strong oxidizing agent and heated the lactic acid is decom- 
posed iuto acetic aldehyde and formic acid, according to the equation: 

CH 3 — CH(OH) — CO.OH = CH 3 .CHO + H.CO.OH. 

Practically, then, the test for lactic acid resolves itself into a test for 
acetic aldehyde, which latter can be readily recognized by testing 
with various reagents, notably so with Nessler's reagent. 1 When 
aldehyde is added to such a solution a yellowish-red or red precipi- 
tate results, the exact color depending upon the amount of aldehyde 
present. One part of the latter may still be recognized when diluted 
with 40,000 parts of water. 

An alkaline solution of iodo-potassic iodide may also be advanta- 
geously used. With this solution aldehyde in a dilution of 1 : 20,000 
will still produce a cloudiness, referable to the formation of iodoform, 

1 Two grammes of potassium iodide are dissolved in 50 c.c. of water and treated with iodide of 
mercury, while heating, until some of the latter remains undissolved. Upon cooling the solu- 
tion is diluted with 20 c.c. of water. Two parts of this solution are then treated with 3 parts 
of a concentrated solution of potassium hydrate; any precipitate that may have formed is 
filtered off and the reagent kept in a well-stoppered bottle. 



140 CLINICAL DIAGNOSIS. 

which is readily recognized by its characteristic odor (Lieben's test 
for acetone). 

Method: The filtered gastric juice is tested for the presence of free 
acids with Congo-red (see p. 111). If present, from 10 to 20 c.c. are 
evaporated to a syrup on a water-bath, after the addition of an excess 
of barium carbonate, while the latter is unnecessary in the absence of 
free acids. The syrup is treated with a few drops of phosphoric acid, 
the C0 2 removed by bringing it to the boiling-point once only, when 
it is allowed to cool, and extracted with 100 c.c. of neutral sulphuric 
ether (free from alcohol), by shaking for half an hour. The layer of 
ether is poured off after half an hour, the ether evaporated (no flame), 
the residue taken up with 45 c.c. of water, shaken and filtered, and 
finally treated with 5 c.c. of sulphuric acid and a point-of-a-knifeful 
of the dioxide of manganese in an Erlenmeyer's flask. This is 
closed with a perforated stopper, carrying a glass tube bent to an 
obtuse angle, the longer limb of which passes into a narrow glass 
cylinder containing from 5 to 10 c.c. of Nessler's reagent or a like 
quantity of an alkaline solution of iodo-potassic iodide. If heat 
be now carefully applied, the aldehyde, formed by the oxidation of 
the lactic acid with Mn0 2 and H 2 S0 4 , passes over when the boiling- 
point is reached, causing the precipitation of yellowish-red aldehyde 
of mercury in the tube containing the Nessler's reagent, or of iodo- 
form if the alkaline solution of iodine be employed. This test is 
an accurate one. 

Quantitative Estimation of Lactic Acid According" to Boas's 
Method. The principle already set forth also applies to the quanti- 
tative estimation of lactic acid. 

Solutions required : 

1. A one-tenth normal solution of iodine. 

2. A one-tenth normal solution of sodium arsenite. 

3. Hydrochloric acid (sp. gr. 1.018). 

4. A potassium hydrate solution (56 : 1000). 
Preparation of these solutions : 

1. A normal solution of iodine should contain 126.53 (mol. weight 
of iodine) grammes of iodine in the litre, and a one-tenth normal 
solution, hence, 12.6 grammes. In order to dissolve the iodine, 25 
grammes of potassium iodide are dissolved in about 200 c.c. of dis- 
tilled water and the 12.6 grammes of resublimed iodine added. 
Distilled water is then added to the 1000 c.c. mark. This solution 
requires no further correction. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 141 

2. The one-tenth normal solution of sodium arsenite is prepared 
by dissolving 19.2 grammes of the salt (mol. weight 191.87) in 
about 900 c.c. of distilled water, and the solution brought to the 
proper strength by titrating with it a known number of c.c. of the 
one-tenth normal solution of iodine, as described below, and deter- 
mining the necessary amount of water to be added. 

Method : 10 to 20 c.c. of the filtered gastric juice are first 
treated, as indicated above, viz., evaporated to a syrup after the 
previous addition of BaC0 3 , if free acids be present. A few drops 
of phosphoric acid are added, the C0 2 removed by ebullition, and the 
residue extracted on cooling with 100 c.c. of ether free from alco- 
hol ; the ether is evaporated after separation, the residue taken up 
with 45 c.c. of distilled water, and treated with H 2 S0 4 and Mn0 2 . 
The flask is closed by a doubly perforated stopper ; through one 
aperture a bent tube passes to the distilling-apparatus, and a straight 
tube provided with a piece of rubber tubing, clamped off, through 
the other. The mixture is then distilled until about four fifths of 
the contents have passed over, excessive heat being carefully avoided, 
as otherwise the aldehyde will be decomposed, according to the 
equations : 

I. CH 3 — CH(OH) — CO.OH = CH 3 .CHO -f HCOOH. 

Lactic acid. Aldehyde. Formic acid. 

II. CH 3 .CHO + HCOOH + 20 = CH 3 .COOH + C0 2 + H 2 0. 
Aldehyde. Formic acid. Acetic acid. 

To the distillate, which is best received in a high Erlenmeyer 
flask, well stoppered, 20 c.c. of the one-tenth normal solution of 
iodine are added, mixed with 20 c.c. of the 5.6 per cent, solution of 
potassium hydrate. The mixture is shaken thoroughly and allowed 
to stand for a few minutes in the flask. In order to liberate 
the hypiodite and the iodine in combination with potassium, not used 
in the reaction, 20 c.c. of HC1 and an excess of sodium bicar- 
bonate in substance — some of the latter should remain undissolved 
.at the bottom — are added, and the excess of iodine determined by 
titration with the one-tenth normal solution of sodium arsenite. The 
titration is carried to the point of decolorization, when freshly pre- 
pared starch solution is added, and the mixture again titrated with 
the one-tenth normal solution of iodine until the blue color is perma- 
nent. The number of c.c. of the one-tenth normal solution employed, 
viz., 20, minus the number of c.c. of the one-tenth normal solution 
of Na 3 As0 3 , will then indicate the number of c.c. of the former 



142 CLINICAL DIAGNOSIS. 

required in the formation of iodoform, viz., the amount of lactic acid 
present in 10 or 20 c.c. of gastric juice, as the case may be. As 1 
c.c. of the one-tenth normal solution of iodine has been found to 
indicate the presence of 0.003388 gramme of lactic acid, it is only 
necessary to multiply the number of c.c. used by this figure, and the 
result by ten, in order to obtain the percentage. 

The method described is reliable and sufficiently accurate for 
clinical purposes. At the same time it may be said that no more 
time is required than in an ordinary quantitative estimation of sugar 
by means of Fehling's method, or of HC1 according to the method 
of Martius aud Luttke. 

Boas's rapid method : This method is less accurate than the pre- 
ceding, but may be advantageously employed in the absence of the 
various reagents necessary with the former. Ten c.c. of filtered gas- 
tric juice are treated with a few drops of dilute H 2 S0 4 and the albu- 
min present removed by heat. The filtrate is evaporated to a syrup 
on a water-bath, water added to the original amount, and this again 
evaporated to a small volume, fatty acids being thereby removed. 
The lactic acid remaiuing is now extracted with ether (200 c.c. for 
every 10 c.c. of the gastric juice), the ether evaporated, the residue 
taken up with water, and titrated with a one-tenth normal solution, 
of XaOH, using phenolphthalein as an indicator. As 40 parts by 
weight of NaOH (mol. weight) combine with 90 parts by weight of 
lactic acid (mol. weight), and as 1 c.c. of the one-tenth normal solu- 
tion of XaOH contains 0.004 gramme of XaOH, the amount of 
lactic acid corresponding to the latter is found from the equation : 
40 : 90 :: 0.001 : x ; 40x = 0.360 ; x = 0.009. The value of 1 c.c. 
of the one-tenth normal solution in terms of C 3 H 6 3 is thus 0.009, 
By multiplying the number of c.c. used by this figure the amount 
of lactic acid present in 10 c.c. of gastric juice is readily determined. 
The result multiplied by 10 will then indicate the percentage. 

The Fatty Acids. 

Mode of Formation and Clinical Significance. Unless much 
milk or carbohydrates have been ingested, fatty acids do not occur in 
the gastric contents in physiologic conditions, and it would appear 
from the researches of Boas that their formation is intimately asso- 
ciated with that of lactic acid. After the exhibition of his test-meal 
(see p. 136) he was unable to demonstrate their presence either in 
normal conditions or in various diseases of the stomach, such as 






THE GASTRH JUIi E AND OASTBH ' ( ONTENTS. 143 

chronic gastritis, atony, or dilatation referable to benign causes, etc. 
In carcinoma tatty acids, ju9t as lactic acid, were quite constantly 
found. 

That butyric acid can be derived from lactic acid has been demon- 
strated in milk by Fliigge, the reaction taking place according to 
the equation : 

2(Q,H 6 8 ) = C,HA + 2C0 2 + 4H. 

This observation is probably explained by the fact that most of the 
organisms causing butyric-acid fermentation are anaerobic, while the 
bacillus acidi lactici and the oidinm lactis at the same time eagerly 
absorb oxygen. 

Acetic-acid fermentation, on the other hand, presupposes the pres- 
ence of alcohol, whether introduced into the stomach as such or the 
result of the action of yeast (saccharomyces cerevisire) upon sugar, 
the transformation of alcohol into acetic acid being represented by 

the equation : 

C 2 H 5 OH + 20 = C 2 H 4 2 + H 2 0, 

while the formation of alcohol during the process of fermentation 
from glucose is shown below : 

I. C 6 H 12 6 + 2H 2 = 2C 2 H 6 + 2H 2 C0 3 . 
H. 2H 2 C0 3 = 2H 2 + 2C0 2 . 

It is, hence, necessary, whenever acetic acid is met with in the 
gastric contents, to exclude the existence of alcoholism, as it is only 
then permissible to refer its presence to stagnation and advanced 
decomposition of carbohydrates. 

If the examination be confined to an analysis of the gastric con- 
tents, obtained otherwise than after the exhibition of Boas's or even 
Ewald's test-meal, the diagnosis of pyloric stenosis with dilatation is 
probably always justifiable in the presence of notable quantities of 
butyric acid and acetic acid, while the same observations after a pre- 
vious washing out of the stomach aud the exhibition of Boas's test- 
meal would more strongly suggest carcinoma as the cause of the 
stenosis. 

That butyric acid may occur in the gastric contents when butter 
or fats in general have been ingested is, of course, not surpris- 
ing, and its presence then should be looked upon as a physiologic 
occurrence. At the same time it should not be forgotten that 
butyric acid, just as lactic acid, may possibly have been formed 
in the mouth, and conclusions should, hence, only be drawn when 



144 CLINICAL DIAGNOSIS. 

such sources of error cau be definitely excluded and the amount 
found exceeds mere traces. 

In conclusion, it may be said that in pathologic conditions butyric 
acid is far more frequently encountered in the gastric contents 
than acetic acid, while the significance of the two in the absence of 
alcoholism is the same. 

Tests for Butyric Acid. 1. Butyric acid can usually be recog- 
nized by its odor alone, which is that of rancid butter. Often, 
however, it will be necessary to resort to more definite tests, such as 
the following : 

2. Ten c.c. of filtered gastric juice are extracted with 50 c.c. of 
ether. The ether is evaporated and the residue taken up with a few 
c.c. of water. If a trace of calcium chloride in substance be now 
added, the butyric acid will separate out in the form of small oil- 
droplets, the nature of which is readily recognized by their pungent 
odor. If, instead of adding calcium chloride, a slight excess of 
baryta-water is used, strougly refractive rhombic plates or granular, 
wart-like masses of barium butyrate are obtained upon evapora- 
tion. 

Tests for Acetic Acid. 1. Like butyric acid, acetic acid can 
usually be recognized by its odor. 

2. Ten c.c. of filtered gastric juice are extracted with ether. The 
ether is evaporated, the residue dissolved in a few drops of water, 
and accurately neutralized with a dilute solution of NaOH, sodium 
acetate being formed. If to this a drop or two of a very dilute 
solution of the perchloride of iron be added, a dark-red color results 
in the presence of acetic acid. With nitrate of silver a precipitate 
is obtained which is soluble in hot water. 

Quantitative Estimation of the Fatty Acids. Method of 
Cahn-Mehriug, modified by McNaught : The total acidity is deter- 
mined in 10 c.c. of filtered gastric juice, and the acidity obtained, 
upon titration of another 10 c.c. after evaporation to a syrup, sub- 
tracted from the former, the difference giving the acidity referable to 
fatty acids. 

Quantitative Estimation of the Organic Acids. Method of 
Hehner-Seemann : This method is based upon the observation that 
if a certain amount of a one- tenth normal solution of NaOH be 
added to organic acids and the mixture be evaporated and inciner- 
ated, the organic acids escape as C0 2 , leaving their alkali behind in 
the form of a carbonate, the amount of which can be determined by 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 145 

titrating with a one-tenth normal solution of HCL The amount oi 
physiologically active HC1 can be determined at the same time l>y 
deducting from the total acidity the acidity referable to organic 
acids. 

Method : 10 or 20 c.c. oi' filtered gastric juice are neutralized with 
a one-tenth normal solution of NaOH, evaporated to dryness, and 
incinerated, the application of heat being discontinued as soon as 
the ash has ceased to burn with a luminous flame. The residue is 
taken up with water, and neutralized with a one-tenth normal solu- 
tion oi HCL This is prepared by diluting 146 grammes of HC1 
(sp. gr. 1.14) with distilled water to about 900 c.c, when the solu- 
tion is brought to its proper strength by comparing it with a one- 
tenth normal solutiou of NaOH, according to directions given 
elsewhere. The number of c.c. of the one-tenth normal solution of 
HC1 employed multiplied by 0.00365 will give the amount of fatty 
acids, in terms of HC1, contained in the 10 c.c. of gastric juice, 
from which the percentage is readily calculated by multiplying by 
10 or 5, as the case may be. By deducting the number of c.c. 
employed from that of the one-tenth normal solution of NaOH first 
used, the number of c.c. of the latter required for the neutralization 
of the physiologically active HC1 is ascertained, and the amount of 
the HC1 determined by multiplying by 0.00365. 

Gases. 

The stomach always contains a certain quantity of gases which 
have partly been swallowed and partly passed into the stomach from 
the duodenum. As fermentative processes in physiologic conditions 
occur only when carbohydrates or fats have been ingested, and 
then only to a slight degree, nitrogen, oxygen, and carbon dioxide 
are the only gases found during the process of albuminous digestion. 
As the oxygen swallowed is, moreover, largely absorbed by the blood, 
and two volumes of carbon dioxide are returned for one volume of 
oxygen, the presence of large amounts of the former and small 
amounts of the latter is readily explained. In an analysis of the 
gases contained in the stomach of a dog which had been fed on meat 
Planer found the following proportions : 

CO, 25.2 vol. per cent. 

O (5.1 " 

X 68.7 " 

10 



146 OLINICAZ DIAGNOSIS. 

"With a strictly vegetable diet, on the other hand, hydrogen may 
also be found (Planer) : 





.via 


n. 


Dog. 


00 2 . 


. 20.79 


33.83 


32.9 vol. per cent. 







0.37 


0.8 •• 


N . 


. 72,50 


38.22 


66.3 •' 


H . 


. 6.71 


27.58 





The presence of H is readily understood if it be remembered that 
during the process of butyric-acid fermentation H and C0 2 are 
formed. Lactic-acid or acetic-acid fermentation does not give rise 
to the formation of gases. 

Marsh eras, CH 4 . a product of the fermentation of cellulose, may 
also be found in pathologic conditions, formed according to the 
equation : 

(C 6 H 10 O 5 )n - (H,0)n = 3(CO-)n + 3(CHJn. 

It is yet an open question whether CH 4 is formed in the stomach 
or passes into the stomach from the small intestine. 

Such observations must, however, be regarded as rarities. In one 
case of this kind, examined by Ewald and Ruppstein, in which 
alcohol, acetic acid, lactic acid, and butyric acid were found in the 
vomited material, an analysis of the gases gave the following result i 

C0 2 20.6 vol. per cent. 

O " 6.5 " 

X 41.4 " 

H 20.6 "' 

CH 4 10.8 " 

Traces of olefiant gas and of sulphuretted hydrogen were also 
found. It is curious to note that in this case the patient, who, accord- 
ing to his own statement, had " acetic acid works in his stomach 
on one day and gas works on another day/' was occasionally able to 
light the eructated gas at the end of a cigar-holder, where it burnt 
with a faintly luminous flame. 

Ammonia and sulphuretted hydrogen are also at times met with, 
and are always rine to albuminous putrefaction. 

To obtain a knowledge of the gases formed in the stomach during 
the process of digestion it is only necessary to fill an ordinary 
Doremus's ureometer, or an Einhorn's sacchari meter, with the un- 
filtered gastric contents, and keep it at a temperature of from 37° 



THE GASTRIC JUICE AND QASTBIi CONTENTS. 147 

to 17° C, when the evolution of gas can l>e closely followed and 
the necessary tests made. The presence of CO s is readily recog- 
nized by passing a small amount of NaOH, in concentrated solution 
or in substance, into the tube, alter the evolution has entirely ceased, 
when the fluid will rise. If other gases be present at the same 
time, these will remain after the C0 2 has been absorbed. H 2 S is 
readily recognized by its odor and by the fact that it will color a 
piece of filter-paper moistened with a few drops of NaOH and 
acetate of lead a more or less pronounced brown. The test is con- 
veniently made by filling a test-tube about half full with the gastric 
contents and closing it with a cork-stopper, to which a strip of lead- 
paper, prepared as indicated, is fastened. 

The eructation of gas from the stomach should not be confounded 
with the so-called eructatio nervosa, in which either no gas is 
eructated, or air simply enters the oesophagus and is expelled again 
with a loud, explosive noise. This may be frequently observed in 
neurasthenic and hysterical individuals, and is to a greater or less 
degree under the control of the will. It is hardly likely, however, 
that the physician will be called upon in the laboratory to differen- 
tiate between this form and that of true ructus caused by fermen- 
tative processes taking place in the stomach. The gases brought up 
in the former conditions are without odor or taste, and thus differ 
from those found in true dyspepsia. 

Acetone. 

The presence of acetone in the gastric contents in pathologic 
conditions has been repeatedly observed, especially by von Jaksch 
and Lorenz, and it is curious to note that the latter was at times 
able to demonstrate larger quantities of the substance in the gastric 
contents than in the urine. 

In the chapter on Acetonuria the relation existing between diges- 
tive diseases and the elimination of acetone will be dealt with more 
fully, but it may here be mentioned that in the " primary " diseases 
of the gastro-intestinal tract acetone is quite constantly met with in 
the gastric contents, while this is but rarely the case in the secondary 
forms, and is never seen in the gastric neuroses. 

In order to test for acetone the gastric contents are distilled after 
the previous addition of a small amount of phosphoric acid (1 : 1000), 
in order to prevent an excessive evolution of gases, and the tests of 



!48 CLINICAL DIAGNOSIS. 

Reynolds and Gunning (see Urine) applied to the distillate. If both 
reactions furnish a positive result, the presence of acetone may be 
regarded as demonstrated. 

Ptomaines and Toxalbumins. 

Remembering that ptomaines and toxalbumins have been directly 
obtained from tainted meat, sausage, fish, clams, crabs, cheese, etc., 
it is probable and, indeed, to be expected that these bodies should 
be present in the gastric contents also. At the same time it may be 
mentioned that the stomach appears to possess the power of eliminat- 
ing from the system poisons of this nature which are circulating in 
the blood. This is shown by the observations of Alt, who found 
that the water with which the stomach of an animal had been irri- 
gated after the subcutaneous injection of the poison of Pelias berus 
and Echidna arictans, or the direct bite of the snake, produced 
the same symptoms of poisoning when injected into another animal. 
It is interesting to note that with lavage of the stomach the poisoned 
animal recovered. Similar observations have been made in cholera 
asiatica. Certain vegetable alkaloids, such as morphine, are also 
known to be eliminated to a large extent by the stomach. 

Vomited Material. 

Food-material. The vomiting of large amounts of totally 
undigested meat two to three hours after its ingestion is a rare 
occurrence, and is only met with in conditions associated with 
an entire absence of digestive power in the stomach ; i. e., in 
cases of atrophic cirrhosis of the stomach (anadeny of Ewald). 
This condition is not to be confounded with the regurgitation of 
undigested food, mixed with mucus and saliva, seen in cases of stric- 
ture of the oesophagus or of the cardiac orifice of the stomach. 
While at the outset of the later disease the regurgitation of food 
occurs immediately or at least very soon after a meal, it may take 
place between meals in the later stages of the disease. The recog- 
nition of the origin of the material brought up may then be exceed- 
ingly difficult. In such cases an examination should be made for 
biliary coloring-matter, which, if present, will, of course, imme- 
diately exclude the oesophagus as the source of the material ejected. 
Unfortunately, however, the reverse does not hold good. Small 
amounts of undigested meat are of no significance. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 



149 



The vomiting of well-digested food is observed in some of the 
neuroses of the stomach, and also in certain cases of acute and 
subacute gastritis, ulcer of the stomach, and chronic gastritis in its 

early stages. The vomiting referable to cerebral and spinal diseases 
also belongs to this category. 

Fig. 34. 




Collective view of vomited matter. (Eye-pieces III., objective 8 A, Reichert.) a, muscle-fibres; 
b, white blood-corpuscles ; c, c', squamous epithelium ; c", columnar epithelium ; d, starch- 
grains, mostly changed by the action of the digestive juices; e, fat-globules ; /, sarcinre ventri- 
culi ; g, yeast-fungi ; h, forms resembling the comma-bacillus found by the author once in the 
vomit of intestinal obstruction ; i, various micro-organisms, such as bacilli and micrococci; 
fc, iat-needles, between them connective-tissue derived from the food ; ?, vegetable cells. 
(v. Jaksch.) 



In this connection it is very important to inquire into the existence 
of nausea previous to the vomiting, for, as is well known, consid- 
erable amounts of saliva and mucus may be swallowed if much nau- 
sea has existed, the result being that the process of digestion is 
arrested before the occurrence of vomiting, when it would be entirely 
erroneous to conclude that, because the material ejected has not 
reached that stage of digestion which should be expected at the time 
of the vomiting, the stomach is incapable of properly performing its 
functions. 

Mucus. The constant presence of large amouuts of mucus in the 
gastric contents, obtained with the stomach-tube, is almost pathogno- 
monic of the mucous form of gastritis, while its presence in vomited 
matter may be referable to its having been swallowed, owing to the pre- 
existent nausea. In cases of pharyngitis moderate amouuts of mucus 



150 CLINICAL DIAGNOSIS. 

are frequently found. The vomiting of pure mucus, according to 
Boas, is always pathognomonic of the absence of dilatation of the 
stomach, a statement founded on reason, as it is altogether unlikely 
that no particles of food should be brought up at the same time. 
Mucus is readily recognized on simple inspection by its glossy 
appearance. Chemically it is distinguished by its behavior toward 
acetic acid. (See Urine.) 

Saliva. The vomiting of pure saliva in the morning upon rising 
is a fairly common symptom of chronic pharyngitis, which in turn 
frequently carries in its trail a chronic gastritis, constituting the so- 
called vomitus matutinus. Saliva, like mucus, is, of course, always 
present in the gastric contents in small amounts. Larger amounts 
are usually referable to an increased secretion and a swallowing of 
the same, owing to the existence of nausea. Chemically, saliva is 
best recognized by testing for the presence of sulphocyanides (see 
Saliva, p. 87). 

Bile. Bile is rarely observed in the gastric contents brought 
up by the stomach-tube, but is frequently seen in vomited matter, 
of which it may be said to be a constant constituent whenever 
the vomiting has been very intense or frequently repeated. Its 
presence in the former case should always excite suspicion of the 
existence of a stenosis of the descending or horizontal portion of 
the duodenum, or the beginning of the jejunum. This diagnosis 
becomes the more probable the more constant its presence. 

Pancreatic Juice. Mixed with bile, there is probably always 
present some pancreatic juice, and it has even been suggested that 
the constant absence of the constituents of this, associated with the 
presence of bile, is strongly suggestive of pancreatic disease or of 
obstruction of the pancreatic duct (the ductus Wirsungianus), 

Blood. The presence of unaltered blood in the gastric contents 
is usually recognized without difficulty. As this, however, may 
undergo marked alterations in color, varying from a deep black to 
a coffee or chocolate-color, owing to the action of any free acid pres- 
ent at the time, the oxyhemoglobin being thereby transformed into 
hseniatin, recourse must, at times, be had to a more detailed chemical 
and microscopic examination, which will clear up existing doubts 
(see Blood, p. 37). It may be stated, as a general rule, that the 
greater the loss of blood, and the shorter the time that it has 
remained in contact with the gastric juice, the less will be its altera- 



THE GASTRIC JUICE AND OA 8 TRIi ' < 'ON TENTS. 1 51 

tion in character. If, furthermore, the blood on standing does 
not undergo very decided alterations in color, the absence of marked 
amounts of acid may be inferred. 

Hemorrhage from the stomach, hcematemesis, may be observed in the 
most divers conditions, being either dependent upon a primary disease 
of the organ, such as nicer and carcinoma, or occurring secondarily 
to diseases of other organs, leading to a hypersemic condition of the 
gastric mucosa, such as the various forms of cardiac, renal, and 
hepatic disease, in connection with menstrual abnormalities, etc. In 
mela?na, purpura hemorrhagica, pernicious ansemia, etc., the cause 
of the hemorrhage cannot always be determined ; it appears to be 
certain, however, that nervous influences may also take part in the 
causation of gastric hemorrhage. 

Pus. The occurrence of pus in the vomited matter, referable to 
disease of the stomach itself, is quite rare, and practically only 
seen in cases of phlegmonous and diphtheritic gastritis. More fre- 
quently it indicates the perforation into the stomach of an accumu- 
lation of pus from a neighboring organ. An abscess of the liver, a 
suppurative pancreatitis, an abscess of the colon may thus prove to 
be the primary source of the pus. When present in considerable 
amount pus is, of course, readily detected by the naked eye ; if 
any doubt should arise, a microscopic examination will determine 
the question. 

Stercoraceous Material. Very important from a clinical stand- 
point is the vomiting of stercoraceous matter, which is notably 
observed in cases of ileus. This is usually recognized without diffi- 
culty by its odor, referable to the presence of skatol. If, however, 
any doubt should arise, it is only necessary to distill the vomited 
matter after the additiou of a little phosphoric acid, and to test for the 
presence of phenol, indol, and skatol in the distillate, as described 
in the chapter on Feces (see p. 169). When chiefly derived from the 
small intestine the vomited matter, according to von Jaksch, will 
contain bile-acids and bile-pigment together with an abundance of 
fat, which may be detected by chemical or microscopic examination. 
The reaction is usually alkaline or feebly acid. 

Quite recently the author had occasion to examine the vomited 
matter of a patient in whom an almost complete obstruction existed 
immediately above the ileo-csecal valve ; the color of the material 
was a golden-yellow, the reaction neutral ; no bile-pigments or 
biliary acids were found, while hydrobilirubin was demonstrated. 



152 CLINICAL DIAGNOSIS. 

Formed masses of feces, if found at all in the vomited matter under 
such conditions, are certainly of extreme rarity. 

Parasites. Of parasites, ascarides, segments of tamia?, trichina?, 
anchylostomum duodenale, and oxyuris vermicularis are, at times, 
encountered, for a description of which see the chapter on Feces. 

The Odor. But little information, as a rule, is derived from the 
odor of the gastric contents. The odor of normal gastric juice 
is quite characteristic, suggesting the presence of some acid, 
which can be sharply distinguished, however, from the well-known 
odor referable to the presence of acetic acid or butyric acid. If 
blood be present in large amounts, the vomited matter emits an odor 
which is so characteristic as never to be mistaken. A feculent odor is 
met with in cases of enterostenosis, or in the presence of an abnormal 
communication between the stomach and the small or large intestine. 
A putrid odor may be observed in cases of ulcerative carcinoma, 
pyloric stenosis referable to ulcer, simple carcinoma of the stomach, 
muscular hypertrophy of the pylorus, stenosis due to inflammatory 
adhesions, etc. 

It may finally be mentioned that in cases of phosphorus-poisoning 
the vomited matter emits an odor of garlic ; the odor observed in 
uremic conditions is referable to ammonia ; a carbolic-acid odor is 
met with in cases of poisoning with this substance. 



MICROSCOPIC EXAMINATION OF THE GASTRIC 

CONTENTS. 

In the gastric juice obtained from the non-digesting stomach the 
various morphologic constituents of mucus and saliva, which have 
been described elsewhere, are found. Microscopic particles of food, 
such as elastic tissue-fibres, starch-granules, fat-droplets, fatty acid 
crystals, vegetable and muscle fibres, are, furthermore, quite con- 
stantly seen. Leucocytes and isolated nuclei are also observed, the 
latter resulting from the action of the gastric juice upon mucous 
corpuscles and epithelial cells. 

If gastric juice be allowed to stand, small tapioca-like bodies will 
collect at the bottom of the vessel, which upon microscopic exam- 
ination will be seen to contain numerous snail-shell-like formations, 
occurring either singly or collected in groups. These probably con- 



THE GASTRIC J rich' AND GASTRIC CONTENTS. 153 

Bist ol altered mucin, as they can be artificially produced by adding 

a sufficient amount of dilute IIC1 to saliva. According to Boas, 
they are of no diagnostic significance. 

Epithelial cells, fragments of the epithelial lining of the ducts of 
glands, as well as goblet cells, arc not infrequently met with in 
the juice obtained from the non-digesting organ. In addition to 
these constituents various micro-organisms, such as the leptothrix 
buccalis, bacillus subtilis, saccharomyces, micrococci, often arranged 
in the form of oetahedra, Clostridium butyricum, etc., may be 
encountered. 

In vomited material containing biliary coloring-matter, leucin, 
ty rosin, and cholesterin are also quite commonly observed, and may 
be recognized by the form of their crystals, as well as their chemical 
reactions, described elsewhere. 

In pathologic conditions sarcinse, blood, pus, shreds of the mucous 
membrane of the stomach, carcinomatous material, etc., may also be 
present. 

Sarcince (Fig. 34) occur in the form of peculiar colonies of cocci, 
arrauged in squares or tetrahedra, strongly resembling cotton-bales. 
Not infrequently they are encountered under normal conditions, but 
only in small numbers, however. In pathologic conditions, on the 
other hand, a drop of the gastric contents may constitute an almost 
pure culture. A case is even on record in which the pylorus had 
become entirely occluded owing to the presence of an inspissated 
mass of these organisms. Whenever present the existence of certain 
fermentative processes may be inferred. 

The occurrence of blood and pus in the gastric contents has been 
considered (see p. 150). 

It not infrequently happens that small shreds of mucous mem- 
brane are brought away by the stomach-tube, especially in cases 
of chronic gastritis, hyperchlorhydry not dependent upon ulcer, and 
the neuroses. Boas even suggests that in the latter case, where frag- 
ments of mucous membrane are so readily detached, this may possi- 
bly be etiological ly connected with the formation of ulcers, as the 
mere action of the abdominal muscles exerted during the process of 
defecation may be sufficient to detach such fragments. From the 
microscopic appearance of these particles it is clear that the diagnosis 
between a gastric neurosis and one of the various forms of chronic 
gastritis may frequently be made, and the same may be said to hold 
good for the differential diaguosis between a true gastritis and a 



154 



CL IXICAL DIA GNOSIS. 



glandular insufficiency, referable to passive congestion of the gastric 
mucosa. 

In rare cases tumor-particles have been found in the gastric con- 
tents, thus permitting of a definite diagnosis during life. In the 



Fig. 35. 






fe 






t m 



:~l 



% 



If 




Cancer-cells from the gastric contents. (Ewald.) 

accompanying illustration (Fig. 35) a specimen obtained from a 
carcinomatous patient is represented, which is quite readily distin- 



FlG. 




A fragment of mucous membrane derived from the stomach. (Ewald.) 



guished upon closer examination from similar fragments of mucous 
membrane (Fig. 36). 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 155 



EXAMINATION OP THE MOTOR POWER OF THE 
STOMACH. 

Under physiologic conditions the stomach should contain but few 
particles of food, or none at all, six hours alter the ingestion of 
Riegel's meal, or one and one-half to one and three-quarters hours 
after that of Ewald. A delay in the removal of the gastric contents 
may be referable to the existence of a simple atony or to dilatation 
of the stomach. According to Boas, an atony may usually be diag- 
nosed, if, following the exhibition of a supper consisting of bread 
and butter, cold meat, and a large cupful of tea, the stomach be 
found empty in the morning, providing, of course, that symptoms 
exist which point to atony or dilatation. It should be remem- 
bered, however, that in cases of acute and subacute gastritis, in 
the absence of a more serious lesion, food may be found in the 
stomach twenty-four hours after its ingestion. A dilatation may, 
on the other hand, be diagnosed if the stomach under the same 
conditions contains considerable food. In such cases it happens 
that not only remnants of the test-supper, but remains of meals 
taken one, two, three, or even more days previously are found. 
The quantities, moreover, which may be obtained at the time of the 
examination are often surprisingly great, and may amount to sixteen 
pounds or more. Portel cites the case of the Due de Chausnes, one 
of Paris' s greatest gourmands, whose stomach could hold 4.5 liters ; 
i. e. 9 8 pints. 

The following methods may be employed for the purpose of test- 
ing the motor power of the stomach : 

Leube's Method. The stomach is washed out six hours after 
the ingestion of Riegel's meal with about 1000 c.c. of water. In 
the presence of only slight traces of food the motor power of the 
stomach may be regarded as normal. This method is undoubtedly 
the most convenient for practical purposes. 

The Salol Test of Ewald and Sievers. This test is based 
upon the observation that salol, a compound ether of salicylic acid, 
is only decomposed into phenol and salicylic acid in an alkaline 
medium. As the salicylic acid is eliminated in the urine as 
salicyluric acid, it is possible by testing the latter to determine the 
time of the passage of the salol from the stomach into the small 
intestine. 



156 CLINICAL DIAGNOSIS. 

A capsule containing one gramme of salol is given to the patient 
immediately after his breakfast or dinner, when separate portions of 
urine, passed one-half, one hour, two hours, and twenty-four hours 
later, are tested by the addition of a small amount of a solution of 
the sesquichloride of iron. In the presence of salicyluric acid a 
violet color results. Under normal conditions a positive reaction is 
obtained after from forty-five to seventy-five minutes. A further 
delay may usually be regarded as indicating the existence of motor 
insufficiency. If no result is obtained after twenty -four hours, a 
pyloric stenosis undoubtedly exists. Under normal conditions, fur- 
thermore, it will be observed that the salol elimination is completed 
after twenty-four hours, while in cases of dilatation of the stomach 
a positive reaction may still be obtained after thirty hours. It is 
thus possible to distinguish between dilatation and descent of the 
stomach. 

The test, while it is convenient and usually yields fair results, is 
not altogether reliable, as the decomposition of the salol may, at 
times, occur in the stomach owing to the presence of alkaline mucus^ 
or may be delayed in the intestines owing to the existence of acid 
fermentation, etc. 

EXAMINATION OP THE RESORPTIVE POWER OF THE 

STOMACH. 

To this end a capsule containing 0.2 gramme of potassium iodide 
is given to the patient shortly before a meal, and the saliva examined 
for the presence of potassium iodide at intervals of from two to three 
minutes. (See Saliva, p. 89.) 

Under normal conditions a violet color is obtained after from six 
and one-half to eleven minutes, and a bluish tinge after from seven 
and one-half to fifteen minutes. In pathologic conditions a delayed 
reaction is observed in almost all diseases of the stomach, which 
is especially marked in cases of dilatation and carcinoma, less so in 
chronic gastritis, and variable in cases of ulcer. 

Absolute conclusions cannot be drawn from results thus obtained, 
however, as a normal reaction-time has also been observed in cases 
of dilatation and chronic gastritis. 



THE GASTBK JUICE AND GASTRIC CONTENTS. 157 

INDIRECT EXAMINATION OF THE GASTRIC JUICE. 

GtJNZBURG's Method. In those cases in which for any reason 
the introduction of the stomach-tube is contraindicated or imprac- 
ticable the following method, suggested by Gunzburg, may be 
employed: 

A tablet of 0.2 to 0.3 gramme of potassium iodide is inserted 
into a piece of the thinnest possible, strongly vulcanized rubber- 
tubing, measuring about 2.5 cm. in length. The ends are folded 
as shown in Fig. 37, and the little package tied with three threads 

Fig. 37. 




A fibrin potassium-iodide package of Gunzburg. 

of fibrin hardened in alcohol. Every package should be examined 
before use, by immersion in warm water for several hours, to deter- 
mine its tightness, testing for the presence of potassium iodide by 
means of starch-paper and fuming nitric acid. One of these pack- 
ages is swallowed by the patient three-quarters to one hour after 
an Ewald's test-breakfast, and the saliva tested for potassium iodide 
at intervals of fifteen minutes, until a positive result is reached, 
or until six hours have elapsed. It is unnecessary to wait longer 
than six hours. In the presence of free HC1 the threads of fibrin 
are dissolved and the potassium iodide absorbed. Under normal 
conditions a positive reaction is obtained after from one to one and 
three-quarters hours, while anachlorhydry undoubtedly exists if no 
result is obtained within five to six hours. In cases of hyper- 
chlorhydry and hypochlorhydry the reaction is delayed for more 
than two to three hours. Gunzburg further advises that the resorp- 
tion-test with potassium iodide be also made, and that the reaction- 
time be deducted from that taken up in the elimination of the iodide 
contained in the package. Several tests, moreover, should be made 
in the same case. 

The author has had occasion to experiment with packages obtained 
from Germany, and manufactured according to the directions of 
Gunzburg. lu most of the packages the threads of fibrin had be- 
come brittle and were broken in transit. The results obtained with 



158 CLINICAL DIAGNOSIS. 

about twenty intact specimens, however, were entirely satisfactory, 
and it is to be regretted that the packages cannot as yet be obtained 
in the American market. 

The Author's Test. Recent researches have led the author to 
believe that a close relation exists between the elimination of indican 
in the urine and the amount of free HC1 present in the gastric con- 
tents. The results reached may be summarized as follows: 

1. Euchlorhydry is never associated with an increased elimination 
of indican. 

2. In cases of simple neurotic hyperchlorhydry a subnormal or 
normal amount of indican is found. 

3. In cases of hyperchlorhydry associated with ulcer an increased 
indicanuria is quite constantly observed. 

4. Anachlorhydry, referable to organic lesions of the stomach, is 
almost invariably associated with a highly increased indicanuria. 

5. Hysterical anachlorhydry may be associated with the elimina- 
tion of a normal or increased amount of indican. 

6. In cases of hypochlorhydry increased indicanuria is the rule. 
Given as premises: 

1. That a resorption of decomposing pus is not taking place any- 
where within the body, as such a process in itself is capable of caus- 
ing an increased elimination of indican. 

2. That a stenosis cf the small intestine does not exist. 

3. A normal mixed diet, containing no excessive amounts of red 
meat. 

The urine of twenty-four hours is carefully collected and a speci- 
men taken therefrom for examination. A few c.c. of urine are mixed 
with an equal amount of concentrated hydrochloric acid, and two 
or three drops of a concentrated solution of sodium hypochlorite 
and 1 or 2 c.c. of chloroform added. The mixture is thoroughly 
agitated and set aside. The indigo which has been liberated in this 
manner is taken up by the chloroform, coloring this blue to a greater 
or less extent, the degree of increase as compared with the normal 
being determined by the intensity of the color obtained. Fpr the 
sake of comparison, it is well to employ the same quantities of urine 
and of reagents in every case, marked tubes beiug very convenient for 
this purpose. 



THE GASTRIC JUICE AND GASTRIC CONTENTS. 



159 



•a 

■A 

o 

1 


Partly digested loud ; mu- 

bai terla ; a few i 
puscles. 

Partly dig) ited (bod ; at 

times shreds uf inn. OUS 

membrane. 

Undigesti d rood . i. 
mucous membrane. 

Undigested food ; no mor- 
phologic w 
menta, 

[f blood be present, this 

usually occurs in the form 

of amorphous me 

pigment ; well-pn 
i. .1 coi push les M 
exceptionally 

Numerous oil 
iams ; bau h ria at d 

fungi. 

Blood present ;it times ; 
sarcimc present in large 
numl 


Fermi 


ferments diminiahed; 
proenzymes pn -■ at, 

Ferments diminiahed; 

proenzymes pr< ant. 

Ferments almost ab- 
sent ; proenzymes 
diminiahed. 

Ferments absent ; 

proenzymes absent. 

Ferments and proen- 
zymes in normal 
amount. 

Ferments and proen- 
zymes usually pres- 
ent. 

Ferments and proen- 
zymes frequently 
absent. 


Fatty acids. 


Often large amounts 

aftera meal, other- 
wise absent. 

I 'resent at times af- 
ter Ewald's test" 
breakfast ; absent 
after that of Boas. 

Absent after Boas's 
test-breakfast. 

Absent after Boas's 
test- break fast. 

Absent. 

Large amounts at 
times after 
Ewald's test- 
breakfast ; absent 
after that of Boas. 

Usually present in 
large amount. 


I 

1 =2 


Absent, or present 
in traces only. 

Traces after Ewald's 
tost-breakfast ; ab- 
sent after that of 
Boas. 

Absent after Boas's 
test-breakfast. 

Absent after Boas's 
test-breakfast. 

Absent after Boas's 
test-breakfast. 

Absent after Boas's 
test-breakfast. 

Usually present in 
large amounts. 


Free 11 CI. 


Diminished or ab- 
sent. 

Usually absont. 

Absent. 

Frequently in- 
creased. 

Diminished or in- 
creased ; more fre- 
quently increased. 

Absent or dimin- 
ished, unless the 
carcinoma has de- 
veloped from the 
base of an old ul- 
cer, when it may 
be increased. 


Reaction, 


Feebly acid. 

Acidity never 
increased. 

Slightly acid or 
neutral. 

Neutnil or alka- 
line. 

Usually in- 
creased acidity. 

Acidity normal 
or Bomewhat 

increased. 

Acidity below 
normal. 


l ®" 
i g 

! S 

5 
| 

jj 

a 
o 
O 


Partly digested 
food : iinicus ; 
frequently a green 

color referable to 
bile-pigment. 

Imperfectly digested 
food; biliary color- 
ing - matter fre- 
quently present; 
not much mucus. 

Imperfectly digested 
food ; much mu- 
cus. 

Unaltered food ; no 
mucus. 

Blood frequently 
present. 

Particles of un- 
digested food in 
various stages of 
decomposition. 

The vomited matter 
has at times the 
appearance of cof- 
fee-grounds. 


i o" 


Acuto gastritis. 

Simple chronic 
gastritis. 

Mucous gastritis. 

Chronic atrophic 
gastritis. 

Gastric ulcer. 

Dilatation of the 
stomach, not re- 
ferable to car- 
cinoma. 

Carcinoma. 



CHAPTEE IV. 

THE FECES. 

DEFINITION. 

The feces may be defined as being a mixture of undigested par- 
ticles of food and unabsorbed secretions of the gastro-intestinal tract, 
together with intestinal mucus, epithelial cells, and bacteria. 

THE EXAMINATION OP NORMAL FECES. 
General Characteristics. 

Number of Stools. The number of stools in the twenty-four 
hours may vary within very wide limits ; as a rule, one or two 
stools pro die may be regarded as normal. Persons are not infre- 
quently met with who have but one stool every two to four days, 
and cases are on record in which only one passage occurred every 
seven to fourteen days, and even every six to eight weeks, the indi- 
viduals enjoying perfect health, as far as could be ascertained. One 
case, that of a female, an opium-eater, has been recorded, in which 
only four stools occurred in one year. 

This latter instance, of course, can hardly be considered within 
range of the normal limits, and demonstrates the importance of 
accurately ascertaining the habitual number of stools for years in a 
patient, and not regarding every individual who has but one passage 
every two or three days as a case of constipation, and to be treated as 
such. 

Amount. In some cases, in which more than one or two stools 
occur in the twenty-four hours, it is well to ascertain the amount act- 
ually passed, in order to decide whether or not the person may be 
considered as normal in this respect. The figures given by different 
observers as expressing the total amount vary somewhat, from 100 
to 200 grammes being about the normal. This quantity is increased 
by a diet rich in vegetable and starchy foods, and diminished by one 
rich in animal albumin, so that 60 and 250 grammes may be regarded 



THE FECES. 161 

as the extreme limits in health. Such amounts as 500 and 1000 
grammes, where much indigestible food has been taken, are patho- 
logic. 

Consistence. The consistence of a stool depends essentially upon 
the amount of water present, 75 per cent, being about the normal ; 
it may thus be cylindrical aud firm or mushy. Round, scybalous 
balls are, at times, seen in health, but occur frequently in cases of 
constipation. 

Odor. The repugnant odor of the feces is, to a large extent, due 
to the presence of indol and skatol, products of albuminous decom- 
position ; sulphuretted hydrogen and traces of phosphin may add 
still further to their disagreeable odor. 

Color. The color of the feces varies, according to the nature of 
the food ingested, from light to almost a blackish-brown, a firm stool 
being in general darker in color than a thin stool. In nursing-infants, 
owing to the exclusive ingestion of milk, the color is light yellow. 
Under normal conditions the color is never due to native biliary 
coloring-matter, the presence of this substance being always indic- 
ative of some pathologic process, but is largely dependent upon the 
presence of hydrobilirubin — i. e., reduced bilirubin. It is, further- 
more, influenced by the nature of the food, chlorophyll tending 
to produce a greenish color, starches a yellowish tinge. If much 
blood be present in the food, the feces may be almost black, 
owing to the formation of hsematin. Huckleberries and red wine 
likewise produce a blackish color, chocolate and cocoa a gray ; prep- 
arations of iron, manganese, and bismuth color the feces dark brown 
or black, owing to the formation of the sulphides of these metals ; 
the green color of calomel stools was formerly supposed to be due 
to the formation of a sulphide, but is more likely caused by the 
presence of biliverdin in such stools. Santonin, rheum, and senna 
produce a yellow color. 

Macroscopic Constituents. 

Alimentary Detritus. Upon further examination of the feces 
it is possible to find visible to the naked eye undigested particles of 
food, which are partly indigestible and partly digestible, such as stones 
of cherries, grape-seeds, woody vegetable fibre, the skins of berries, 
large pieces of connective tissue, undigested pieces of apple, pear, 
potato, grains of corn, etc. The latter are found in abundance when 
the food is insufficiently masticated or taken in excessive amounts. 

11 



162 



CLINICAL DIAGNOSIS. 



Foreign Bodies. In children, the insane, cases of hysteria, and 
even in people who are otherwise possessed of their five senses, the 
physician must be prepared to find at tiroes all kinds of foreign 
bodies, such as pins, coins, buttons, false teeth, tooth-plates with 
ragged edges, and even dirk- knives, all of which have been known 
to pass through the alimentary canal with perfect safety ; certainly a 
wonderful fact, when it is remembered that so small and innocent- 
looking an object as a grape-seed may, at times, prove the cause of 
death. It must not be forgotten, however, that in certain cases of 
hysteria bodies may be shown by patients which they claim have 
passed by the rectum, but which have been wilfully added to the 
stools, such as snakes, frogs, etc. 

Microscopic Constituents. 

Constituents Derived from Food. Microscopically indigestible 
and undigested constituents of food may be seen (Fig. 38), such as the 
framework of vegetable material, sometimes still containing starch- 



FlG. 38. 




Collective view of the feces. (Eye-piece in., objective 8 a, Reichert.) a. muscle-fibres; 
6, connective-tissue; c, epithelium; d, white blood-corpuscles; e, spiral cells; /, i, various 
vegetable cells ; k, triple phosphate crystals in a mass of various micro-organisms ; I, diatoms, 
(v. Jaksch.) 



granules or remnants of chlorophyll ; muscle-fibres, often colored 
yellow by biliary pigment and considerably altered in structure, 
being split up partly or entirely into the well-known disks ; elastic- 
tissue fibres are readily recognized by their double contour and bold 
outlines. Connective-tissue fibres of the white fibrous variety can 
also generally be distinguished ; when present in large quantities, 






THE FECES.. L63 



however, they are usually indicative of some digestive derangement, 
link's- they be observed following the ingestion of a meal particularly 
rich in meat. Flakes of casein are also frequently seen. 

The presence of fat is quite common, occurring in the form of 
polygonal masses, as needle-like crystals, and also in droplets. The 
strongly refractive masses are often colored yellow or yellowish-red, 
and may be recognized as fats, fatty acids, or their soaps, from the 
possibility of transforming them into fat-droplets by the addition of 
sulphuric acid and the subsequent application of heat. 

Starch-granules may be found in all stools, and are readily recog- 
nized by treating them under the microscope with a solution of iodo- 
potassie iodide, when the granules will assume a blue color. It has 
been stated above that at times they may be seen enclosed in vege- 
table cells, but such is not the rule. 

Coagulated albumin, numerous fatty acid crystals, and fat-droplets 
can be found in the feces of sucklings. 

Morphologic Elements Derived from the Alimentary Canal. 
Under this heading must be mentioned : 1. Leucocytes, which, how- 
ever, occur in only very small numbers in the normal stool. 2. Epi- 
thelial cells are never very numerous in physiologic conditions, and 
are generally derived from the rectum and anus. Occasionally 
cylindrical epithelial cells, which may or may not be pigmented, and 
usually more or less altered in shape and structure, are seen. The 
various transition-forms from the well-defined cylindrical or goblet 
cell to mere spindles containing no nuclei may thus be found. 
These degenerative changes, according to Nothnagel, are the result 
of the abstraction of water from the cells. 3. The occurrence of 
red blood-corpuscles in a stool in very small numbers, the health of 
the individual being otherwise good, is of no significance. 4. In 
every stool a large number of structureless granules may be seen, 
lying either by themselves or collected into heaps, which are desig- 
nated as detritus. 

Crystals. The crystals of fatty acids and their soaps (Fig. 39), 
usually occurring in the form of needles, must here be mentioned ; 
these are probably calcium and magnesium salts of the higher fatty 
acids. Crystals of oxalate of lime are observed, especially after 
a meal rich in vegetable matter, and are readily recognized by 
their characteristic form. Lactate of calcium is frequently seen in 
the stools of children, in the form of sheaves composed of radiat- 
ing needles. Calcium carbonate is rarely observed, but occasionally 



164 CLINICAL DIAGNOSIS. 

occurs in the form of amorphous granules or dumb-bell shaped crys- 
tals. Calcium sulphate crystals are likewise rarely observed. Neu- 
tral phosphate of calcium and ammonio-magnesium phosphate crystals 
are often present, and may be readily recognized, the former occurring 
in the form of more or less well-defined wedge-shaped crystals, col- 
lected into rosettes, the latter presenting the well-known coffin-shape. 
Charcot-Leyden crystals — i.e., the phosphate of spermin — may also 
at times be seeu. Hasmatoidin crystals are probably always patho- 
logic. Cholesterin occurs but rarely in crystalline form, while it is 
always present in solution. 

Fig. 39. 

i slit 

Fatty crystals obtained from the feces. 

Parasites. The parasites which occur in normal feces may be 
divided into vegetable and animal parasites. 

Vegetable Parasites. These are often present in enormous 
numbers, and masses may be passed which consist almost entirely of 
them. What relation they bear to the process of digestion is as yet 
an open question. It does not appear very probable to the author, 
however, that their presence is essential to the maintenance of 
normal peristalsis and digestion, as is generally taught. The idea 
held by Pasteur and many others, that animal life cannot go on in 
the absence of bacteria from the digestive tract has recently been 
disproved by Nattall and Tierfelder [Zeibschrifi fur phusiologische 
Oiemie, vol. xxi. p. 109). A guinea-pig removed by Cesarean 
section under antiseptic precautions from the uterus of the mother- 
animal was placed in a sterilized glass cage and nourished for a 
week with sterilized food. The air which the animal breathed was 



THE FECES. 165 

likewise sterilized. During this week the animal consumed about 
330 c.c. of milk ami appeared to be normal in every respect. At 
the expiration of the week it was killed, when a microscopic ex- 
amination of the intestinal contents revealed the entire absence of 
bacteria. Culture-experiments were likewise negative. 

Modern researches have shown that certain bacteria which are 
constantly present in the intestinal tract may, under certain condi- 
tions, assume pathogenic properties. This is true especially of the 
bacillus coli communis. 

Fungi Fungi, with the exception, perhaps, of the o'idium albi- 
cans, which has at times been observed, are but rarely found in the 
feces. 

Schizomiicctes. Saccharomyces cerevisiae belongs to the normal 
constituents, as it were, of the feces, and is found in its characteristic 
forms, three or four buds, however, being but ordinarily observed, 
which, owing to the glycogen present in their substance, assume a 
mahogany color when treated with a solution of iodo-potassic iodide. 
They should not be confounded with a class of bacteria which 
closely resemble the saccharomyces in appearance, but yield a blue 
color with the reagent mentioned (see below). 

Bacteria. The bacteria are the micro-organisms, xazi^o'^u, which 
are found in the feces; they may be divided into two classes: 
Those belonging to the first order are stained a yellow or a yel- 
lowish-brown with iodo-potassic iodide, while those belonging to the 
second class are colored blue or violet by the same reagent. To the 
former belong the bacterium termo, the bacillus subtilis, and a large 
number of micrococci, into a description, of which, however, it is not 
necessary to enter at this place. Under the second heading von 
Jaksch describes the following forms: 

1. Micrococci occurring in the zooglcea stage, which are colored 
a violet-red. 

2. Short, thin rods, tapering slightly at both ends, and in their 
microscopic appearance reminding one very much of the bacillus of 
the septicaemia of mice ; sometimes one or two little bodies, which 
are not stained by the reagent, are found in these. 

3. Short or long rods, which resemble the leptothrix buccalis in 
their behavior toward iodo-potassic iodide. 

4. Bacilli resembling the bacillus subtilis. 

5. Clostridium butyricum. This micro-organism, according to 
Brieger, is the cause of butyric-acid fermentation. It occurs in the 



IQQ CLINICAL DIAGNOSIS. 

i'orm of broad rods with rounded-off extremities, but may also be 
elliptical or spindle-shaped. With LugoFs solution it is colored 
blue or violet either entirely or only in its central portion. 

6. Large round forms, characterized, when unstained, by a pale 
lustre, and which very much resemble yeast-cells (see above). 

7. Micrococci, which assume a reddish, but not a very pronounced 
tiut. 

It should be mentioned that this second class of micro-organisms 
is not so largely represented in the feces as the first. 

The animal parasites which may, under physiologic conditions, be 
present, will be described together with those occurring under abnor- 
mal conditions. 

Chemistry of Normal Feces. 

Reaction. The reaction of the feces is usually alkaline, some- 
times neutral, rarely acid, the alkalinity being due to ammoniacal 
fermentation, the acidity to lactic- and butyric-acid fermentation 
taking place in the intestines. 

General Composition. The following table, taken from Gautier, 
will give an idea of the composition of fresh feces, calculated for 
1000 parts by weight: 

Water 
Solids . 

Total organic material 
Total mineral material 
"Alimentary residue 

The organic material yielded 

Aqueous extract 
Alcoholic extract . 
Ethereal extract . 

In addition, there are gases, which vary considerably in amount 
according to the nature of the food ingested, such articles as beans, 
heavy bread, potatoes, etc., increasing their amount very considerably. 

Milk diet. 

Per cent. 
Carbonic dioxide . . . 9-16 
Hydrogen .... 43-54 
Marsh gas . . . . 0.09 
Nitrogen .... 36-38 45-64 10-19 

1 Including 54 parts of mucin, epithelium, and calcareous salts. 

2 Not comprising earthy phosphates. 

3 Of this, 3.2 cholesterin. 



Adult man. 


Suckling. 


733.00 


851.3 


267.00 


. 148.7 


208.75 


137.1 1 


10.95 2 


13.6 


83.00 




53.40 


53.5 


41.65 


8.20 


30.70 


17.6 3 



Meat diet. 


Vegetable diet 


Per cent. 


Per cent. 


8-13 


21-34 


0.7-3 


1.5-4 


26-37 


44-55 



THE FECES. 167 

Of these gases, C0 2 is referable to alcoholic and butyric-acid fer- 
mentation, as well as to albuminous putrefaction, taking place in 
the intestines. Marsh gas, CH 4 , is similarly formed during the fer- 
mentation of cellulose, while the nitrogen has been partly swallowed 
and is partly referable to albuminous putrefaction. A portion also 
is probably derived form the blood, and it may be mentioned in this 
connection that the enormous quantities of C0 2 so often discharged 
in cases of hysteria are undoubtedly attributable to this source, the 
gas passing from the blood through the gastro-intestinal mucous 
membrane into the stomach and intestines. 

In order to give a general idea of the chemical constituents of the 
feces these may be divided into: 

1. Food-material, which could be assimilated, but which was taken 
in excess, such as starches, fats, and a small amount of non-assimi- 
lated albuminous material. 

2. Indigestible substances, such as chlorophyll, gums, pectic pro- 
ducts, resins, various coloring-matters, nuclein, chitin, and insoluble 
salts, viz., silicates, sulphates, earthy phosphates, ammonio-magne- 
sium phosphate, etc. 

3. Products derived from the digestive canal, as mucus, partly 
transformed biliary acids, dyslysin, cholesterin, lecithin. 

4. Substances in process of absorption, as emulsified fats, fatty 
acids, leucin, and biliary acids. 

5. Products of decomposition, referable to microbic activity ; fatty 
acids, comprising the entire series from acetic to palmitic acid, the 
latter being especially abundant ; butyric and iso-butyric acid, lactic 
acid, phenol, cresol, indol, skatol, excretin, amido-acids and acid- 
amides, leucin and tyrosin, phenyl-proprionic, phenyl-acetic, hydro- 
paracumaric, and parahydroxylphenyl-acetic acid, ammonium carbon- 
ate and ammonium sulphide. 

6. Pigments: stercobilin, hsematin, hydrobilirubin, coloring-mat- 
ters derived from the blood, and, in abnormal conditions, bile- 
pigments. 

7. Water. 

8. Gases, as C0 2 , CH 4 , H, and N. 

The study of these substances as a whole, as well as in detail, is 
of considerable importance, not only from the standpoint of the phys- 
iologist, but also from that of the clinician, giving, together with a 
careful urinary analysis, the clearest idea of the metabolic processes 
taking place in the body. 



Igg CLINICAL DIAGNOSIS. 

The chemical study of the feces has not so far received the atten- 
tion which it deserves, and data of but little practical importance 
have been obtained from the work accomplished. This field will, 
without doubt, furnish highly important results in the course of 
time, those gained in the microscopy of the feces being certainly of 
a nature to encourage a detailed chemical study of the same. Up 
to the beginning of the eighties the morphologic and bacteriologic 
study of the feces had been similarly neglected, but brilliant results 
have been achieved within the last few years. It is only necessary to 
recall the discovery of the cholera bacillus by Koch in 1884 ; of the 
amoeba coli by Losch and Kartulis, and its relation to tropical dysen- 
tery ; the relation of bothriocephalus latus and anchylostomum 
duodenale to certain forms of severe anemia ; not to speak of 
the generally recognized importance which the examination of the 
feces for the eggs of parasites in general has assumed within late 
years. 

It is impossible to give here a detailed description of the various 
chemical constituents which have been mentioned. Only the most 
important ones and those especially interesting from a physiologic 
and pathologic standpoint will be considered. 

Phenol, Indol, and Skatol. Tyrosin, produced during the pro- 
cess of albuminous putrefaction, and also during tryptic digestion, 
must be regarded as the mother-substance of phenol, cresol, indol, 
and skatol. It may be represented by the formula: 

/CH 2 — (NH 2 U COOH 
C«H 4 = C 9 H n N0 3 

\OH 

The relation which phenol, cresol, indol, and skatol bear to tyrosin 
may be seen from the following formulae: 

CH 3 

C 

C 6 H 4 CH =- C 9 H 9 N ( Skatol). 
\ / 

XH 

CH 

/% 

C 6 H 4 CH = C 8 H 7 N (Indol). 
\ / 
XH 

C 6 H 4 .CH 3 .OH = C 7 H 8 (Cresol). 

C 6 H 5 .OH = C 6 H 6 (Phenol). 



THE FECES. 169 

As the tyrosin, however, is very readily decomposed, it is usually 
not found in the feces, but the products of its decomposition instead, 
viz., the phenols, indol, and skatol. 

As will be seen more especially in the chapter on Urine, these bodies, 
after having undergone oxidation, unite with sulphuric acid, or, if 
this be not present in sufficient amount, with glycuronic acid, and are 
excreted as phenol, indoxyl, and skatoxyl sulphates or glycuronates 
in the urine. In the feces, on the other hand, phenol, cresol, indol, 
and skatol are found as such. From these they may be obtained in 
the following manner: 

The feces are diluted with water, acidified with phosphoric acid, 
and distilled. The volatile fatty acids present, together with phenol, 
indol, and skatol, pass over. The distillate is then neutralized with 
sodium carbonate and again distilled. During this process phenol, 
indol, and skatol pass over, the fatty acids remaining behind as 
sodium salts. In order to separate the phenol from indol and skatol, 
the distillate is alkalinized with potassium hydrate, and again distilled. 
The phenol now remains behind and may be obtained in pure form 
by distilling with sulphuric acid ; in this final distillate its presence 
may be demonstrated by the following reactions: 

1. With perchloride of iron phenol yields an amethyst- blue color. 

2. With bromine-water a crystalline precipitate of tribromophenol 
results. 

3. Treated with Millon's reagent — i. e., the acid nitrate of mer- 
cury — a red color develops. 

Indol and skatol, on the other hand, pass over after treating the 
above mixture of the three with KOH and distilling. These two 
bodies may then be separated from each other by taking advantage 
of their different degree of solubility in water. 

Indol forms small plates, melting at 52° C, which are easily 
soluble in hot water, alcohol, and ether ; its odor is feculent. 

Reactions of indol: 1. When treated with nitric acid and a little 
sodium nitrite a crystalline red precipitate of the nitrate of nitroso- 
indol is obtained. 2. A small piece of pine-wood, moistened with 
an alcoholic solution of indol, acidified with muriatic acid, is colored 
a cherry-red. 

Skatol also crystallizes in plates, which melt at 95° C. They are 
soluble with more difficulty in water than indol, and emit a feculent 
odor. 

Reactions of skatol: 1. With nitric acid and sodium nitrite only 



170 



CLINICAL DIAGNOSIS. 



a milky cloudiness results. 2. Pure skatol does not yield any color 
with pine-wood moistened with muriatic acid ; but if a bit of the 
wood be saturated with a dilute alcoholic solution of skatol and then 
immersed in strong muriatic acid, it assumes a cherry-red and later 
a bluish-violet color. 3. With nitric acid of a specific gravity of 
1.2 it gives upon boiling a marked xanthoproteic reaction ; i. e., a 
yellow color which turns to orange upon adding an excess of ammonia. 

Finally, the determination of cresol in the presence of phenol, 
together with which it is obtained, is, when only small quantities of 
these substances are present, a difficult matter. They may be sepa- 
rated from each other by transforming both into their sulpho-acids, 
the barium salt of parasulphophenol being practically insoluble in 
barium hydrate. 

Fatty Acids. The fatty acids present in the feces, as well as the 
relation existing between these, are given in the table below. The 
formula C n H 2n+ iCOOH or C n H 2n 2 expresses their general structure: 



Formic acid 


H.COOH .... 


C H 2 2 


Acetic " 


CH 3 COOH .... 


C, H 4 2 


Proprionic acid CH 8 .CH 2 .COOH . 


C 3 H 6 2 


Butyric ' 


CH 3 .(CH 2 ) 2 .COOH 


C 4 H 8 2 


Isobutyric ' 


(CH 3 ) 2 .CH.COOH 


C 4 H 8 2 


Valerianic ' 


CH 3 .(CH 2 ) 3 .COOH 


C 5 H 10 O 2 


Caproic ' 


CH 3 .(CH 2 ) 4 .COOH 


C 6 H12O2 


Capric 


CH 3 .(CH 2 ) 8 .COOH 


^10 *-"- 20^2 


Palmitic ' 


CH 3 .(CH 2 ) u .COOH 


Cl 6 H 32 2 


Stearic " 


CH 3 .(CH 2 ) 16 .COOH 


^18^36^2 



These acids are derived partly from fats, partly from carbohy- 
drates, and to some extent also from proteids. 

Separation of the fatty acids from the feces: If the distillate, neu- 
tralized with sodium cabonate, referred to in the above method 
(p. 169), be again distilled, the sodium salts of the fatty acids 
remain behind, the process taking place being one of saponifica- 
tion ; e.g. : . 

2C 15 H 31 .COOH + Xa 2 C0 3 = 2C 15 H 31 .COO.Na + H 2 + C0 2 . 

The solution is then evaporated to dryness on a water-bath, the 
residue extracted with alcohol, the alcohol evaporated, and the final 
residue dissolved in water. This solution may now be further 
examined. In order to separate the different fatty acids from each 
other, it is best, if the quantity be sufficiently large, to transform 
them into their silver or barium salts, and to separate these by their 
varying degrees of solubility in water, or by fractional distillation. 



THE FECES. 171 

General properties of the fatty acids : They are all monobasic, 
soluble in water, alcohol, and ether. Their alkaline salts are 
readily soluble in water and alcohol, but insoluble in ether. The 
silver salts are dissolved with difficulty. 

1. Formic acid is a colorless liquid, of a penetrating odor, boiling 
at 100° C. A concentrated solution of its alkaline salts is precipi- 
tated by AgN0 3 ; the Ag salt becomes black on standing, and 
reduction takes place at once upon the application of heat. Treated 
with perchloride of iron in a neutral solution it yields a blood-red 
color, which disappears upon boiling, a rust-colored precipitate at 
the same time being formed. 

2. Acetic acid is a liquid of a pungent odor, which boils at 
119° C. Upon neutralization a blood-red color is obtained on the 
addition of perchloride of iron. Neutral solutions of its alkaline 
salts yield a precipitate with nitrate of silver, soluble in hot water, 
without reduction taking place. 

3. Proprionic acid is an oily fluid, boiling at 117° C. With per- 
chloride of iron no red color results ; with silver nitrate it behaves 
like formic acid. 

4. Butyric acid is an oily liquid, having an odor similar to rancid 
butter, boiling at 137° C. Its salts, when treated with an acid, 
give off the characteristic odor ; with perchloride of iron it yields no 
red color ; with AgN0 3 its alkaline salts form a crystalline precip- 
itate insoluble in cold water. 

5. Valerianic acid boils at 176.3° C, and has a penetrating, dis- 
agreeable odor. Its silver salt crystallizes in plates, which are soluble 
with difficulty. 

Cholesterin. Cholesterin (C^H^O) occurs in small amounts in 
almost all animal fluids. It is also found in various tissues of the 
body, especially in the brain. Its origin and mode of formation 
in the various organs of the body, as well as the cause of its pres- 
ence in the alimentary canal, are as yet unknown. It crystallizes 
in colorless, transparent plates, the margins and angles of which 
usually present a ragged appearance (Fig. 40). It is soluble in water, 
dilute acids, and alkalies. In boiling alcohol it is readily soluble, 
crystallizing out from this solution on cooling ; it is likewise very 
soluble in ether, chloroform, and benzol. 

In order to obtain cholesterin from the feces, in which it is always 
present, though rarely in crystalline form, the fatty acids, phenols, 
indol, and skatol must first be distilled off, as described, when the 



172 CLnmcAZ diagnc scs 

: ngly acidified with sulphuric extracted with 

alcohol, and then with ether. The ethereal extract is filtered, the 
ether distilled off. and the residne ligested with carbonate o! sodiam 
I rr to transform any fatty acids which may still be present into 
salts. This mixture is then evaporated to dryness and again 
with ether. The alcoholic extract above mentioned is also 
filtered, supersaturated with s : ilium carbonate, the alcohol distilled 
off. the residue dissolved in water, and likewise rxtraeted with ether. 
In the watery alkaline residue there remain bile acids, oleic, palmitic. 
and stearic acids, which can be separated by transforming them into 
their barium salts. The cholesterin and fats pass over it into the 
ether. This is : s tilled off and the residue treated with an alcoholic 
s:-L'.::: n :: KOH. Tiic :i::::i is :"-::::::::i yi :■.. ^:-'-:-\:--\\. 
the remaining liquid diluted with water and again extracted with 
ether. The fats remain in the aqueous solution as soaps, while the 
cholesterin has issed over into the ethe 

7: :- I 







Cholesterin crystals. 

Testa for cholesterin: 1. Under the microscope add a drop of 
Iphuric acid to some of the crystals : the latter gra - 
ually r. the edges ass ... rilowish-red color. 

2. Dissolve a few crystals in chloroform, add concentrated sul- 
phuric acid and shake the mixture: the chloroform assumes a blood- 
red to a purplish-red color, while the sulphuric acid at the same 
irked flaorescs-. 
solution of soaps obtained above is acidified with dilute sul- 
P ni >™ - .hich have separated out. may 

be filtered or! and identified individually by their boiling-points and 
the analysis of their barium salts. 



THE FECES. 173 

The filtrate finally obtained, when neutralized with ammonium 
hydrate, contains glycerine. 

The Biliary Acids. The biliary acids found in the feces are : 
Glycocholic acid (C 26 H 43 ]S T 6 ), tanrocholic acid (C 26 H 45 NS0 7 ), and 
cholalic acid (C 24 H 4 5 ). 

The two former occur in normal bile, and can be decomposed into 
cholalic acid and glycocoll and cholalic acid and taurin respectively ; 
as this process of decomposition takes place ordinarily in the intes- 
tines, the third acid — i. e., cholalic acid — is always i'ound in the feces. 

In order to demonstrate the biliary acids, the fatty acids, phenols, 
indol, and skatol are first removed by distillation with phosphoric acid. 
The residue is taken up with water and boiled, and the filtered liquid 
precipitated with acetate of lead and a little ammonium hydrate. The 
biliary salts of lead are contained in the precipitate, from which they 
can be removed by washing with water and finally boiling the pre- 
cipitate with alcohol. The washings are then filtered and the lead 
salts transformed into sodium salts by treating the filtrate with 
sodium carbonate. Upon further filtration the filtrate is evaporated 
to dryness and the residue extracted with hot alcohol. Upon evap- 
orating this the salts of the acids sometimes crystallize out as such, 
while more often a dirty amorphous precipitate only is obtained, 
which may be rendered crystalline by treating with ether. The 
amorphous residue, however, can be employed for making the neces- 
sary tests : 

Pettenkoffer's test : A small amount of the substance is dissolved 
in water, and two-thirds of its volume of concentrated sulphuric acid 
added, care being taken that the temperature does not exceed 60° or 
70° C. A 10 per cent, solution of cane-sugar is added, drop by 
drop, stirring constantly. If biliary acids be present, the solution 
assumes a beautiful red color, which upon standing turns a bluish- 
violet. This test depends upon the action of furfurol derived from 
the sulphuric acid and cane-sugar upon the biliary acids. 

Pigments. Among the pigments present in normal feces sterco- 
bilin and hydrobilirubin must be considered. 

Stercobilin is spoken of by Gautier as the principal coloring-matter 
of the feces, derived from bilirubin by a process of reduction. Owing 
to its great similarity to hydrobilirubin it has even been said to be 
identical with this. It has been obtained by extracting the feces 
with acidulated alcohol ; this extract is diluted with water and 
shaken with chloroform, which latter dissolves the pigment. 



174 



CLiyiCAL DIA 7NOSIS. 



. ;e between stercobilin and hudrobilirubin appears to 
oscopic one, the spectrum of the former when treated with 
1 ammonium hydrate giving rise to four bands 
of absorption, while only three are obtained with the latter. The 
pronounced green fluorescence, however, is common to both. 
- Bv means of the spectroscope it is also possible to distinguish 
between normal urobilin and stercobilin : the latter is possibly iden- 
tical with the pathologic urobilin served in febrile urines. 

Hudrobilirubin is identical with the urobilin of Jaffe and the 
febrile urobilin of MacMunn. and shows, as has just been mentioned, 
three be ids :: absorption. Its chemical formula is C : H =: X 4 7 . 
According :: von Jaksch, it is : itained in the same manner as ster- 
cobilin. 

PATHOLOGY OF THE FECES. 

G-eneral Characteristics. 

Number of Stools. As has been pointed out (p. 160). one 
stools lay may be considered as normal: but here as else- 
where the " One man's food, another man's poison." holds 
good. Having lefinitely ietermined in a .Or: ase the number of 
stools in the twenty-four hoars in health, it is possible to state 
whether the particnlai ase may be : as normal in this 
. whether diarrheas istipation exists. 
As the •:::: — :r- t of the stools is in diarrhea, this con- 
t : ne in which too frequent liquid passages 
exist, while the reverse ma; hold good foi ation, 
the c v of the stools in this condition being usually also 
altered. 

The term ob&i m the ither hand, denotes a state of affairs 

in which n are voided. In a general way it mav be said that 

"""hate- stalsis likewise produce 

diarrhoea, and that whir ises diminish peristalsis give rise to 

constipation. In the former condition the numbers: stools may 
vary from one to thirty, forty, or even fifty in the twenty-four 
8 - cholera. The consistence of the stool when only 

one ifl in the twenty-four hours will, of course, decide the 

hetherth :-_ild be regarded as one of diarrhoea or not. 



THE FECES. 175 

One stool passed in the twenty-four hours may under certain condi- 
tions be regarded as a symptom of constipation, but more commonly 
this term is applied to a condition in which a stool occurs only 
every two, three, four or more days, or even weeks or months. 

Consistence. The consistence of the stools may undergo varia- 
tions, which run a course parallel to their number. They may thus 
be thin, mushy, and even watery, which latter condition is met with 
most commonly in cholera asiatica and dysentery, but may also occur 
in any severe enteritis. In constipation, on the other hand, owing 
to an increased absorption of water from the feces, these may be 
passed as very hard and perfectly dry masses, constituting what are 
known as scybala. 

Amount. The absolute amount of feces voided in the twenty- 
four hours bears an inverse relation to the number of stools and their 
consisteuce, providing, of course, that no abnormally large ingestion 
of food has occurred, in which case, an abnormally large stool of 
moderate firmness may be passed. Two exceptions must, however, 
be noted to this rule ; i. e., the passage of large quantities of firm 
feces following an attack of constipation of long duration or an 
attack of severe obstruction. 

Odor. As the normal offensive odor of the feces is largely 
due to products of intestinal putrefaction, an increase in offensiveness 
will naturally be referable to conditions in which the putrefactive 
processes are increased. A most disagreeable odor is thus met with 
in the so-called acholic stools, which may not necessarily be fetid, 
however. The odor of fatty acids is observed in the lighter grades 
of infantile diarrhoea, while a markedly putrid odor is associated with 
its severer forms, referable to increased albuminous putrefaction. A 
very characteristic odor is further noted in the stools of cholera 
and dysentery, OAving to the presence of considerable quantities of 
cadaverin. A horribly rotten stench is present in the gangrenous 
form of dysentery, and in carcinomatous and syphilitic ulcerations 
of the rectum. An ammoniacal odor is due to an admixture with 
urine undergoing ammoniacal decomposition. 

Reaction. The reaction of the stools can hardly be said to be of 
diagnostic significance, unless they be strongly acid or alkaline. In 
infants the stools are normally acid. 

Color. The color of pathologic feces may vary a great deal. 
When unaltered bile, which, as has been mentioned above, is absent 



176 CLINICAL DIAGNOSIS. 

under normal conditions, is present, the stools may assume a golden- 
yellow, a greenish-yellow, or even a green color. In cases of biliary 
obstruction or suppression, on the other hand, they become pasty 
and have a grayish or even white color, which, however, is not so 
much due to the absence of coloring-matter derived from the bile, 
as to an insufficient absorption of fats, as was shown by Strumpell, 
who succeeded in obtaining stools of a light-brown color after feeding 
patients affected with catarrhal jaundice upon a diet containing a 
minimum amount of fat. 

It may be said in general that in diarrhoea the color of the stools 
becomes lighter, tending to yellow, while in constipation the color 
tends to black. 

Perfectly colorless or milky stools are met with in those conditions 
in which in consequence of profuse diarrhoea all fecal matter has been 
washed away, and in which the stools subsequently passed consist of 
serum, as in cholera asiatica, the severe forms of dysentery, and in 
entero-colitis. 

If blood be present, the stools may present a scarlet-red, a dirty 
brownish-red, a coffee, or even a perfectly black color. Adherent 
blood, usually bright-red in color and found on scybalous masses, is 
probably always derived from the rectum or anus, while a change 
in color, indicating an earlier date of the bleeding, usually points 
to the colon. It may be said that whatever the form of the 
stool, be it thin or thick, if unaltered blood be present, the colon, 
rectum, or anus must be regarded as the seat of the hemorrhage, as, 
for example, in cases of hemorrhoids, ulceration of the rectum asso- 
ciated with carcinoma or syphilis, or of the colon in dysentery. 

An intimate admixture of blood with the stool, the color of the for- 
mer being at the same time altered, so as to vary from a brownish- 
red to black (owing to the presence of sulphide of iron), is indicative 
of hemorrhage into the stomach or the small intestine. The darker 
the color of the blood the more remote from the anus will be, as a 
rule, the seat of the hemorrhage. Black or coffee-colored stools are 
thus observed in cases of ulcer of the stomach or of the duodenum, 
in melsena neonatorum, and similar conditions. 

When profuse intestinal hemorrhages take place, however, as in 
some cases of typhoid fever and nielsena, and particularly when 
diarrhoea exists at the same time, as it often does in the former con- 
dition, the blood which appears in the stools may be changed but 
very little or not at all. 



llll' FECES. 177 

An admixture of pus with the Feces in notable amounts also gives 
rise to a characteristic color, as is seen in cases of dysentery, syphil- 
itic and carcinomatous ulceration of the colon and rectum, following 
the perforation of a parametritic or periproctic abscess into the rec- 
tum, etc. 

Green stools are observed especially in infants, and may be refer- 
able to two different causes, being dependent on the one hand upon the 
presence of a bacillus, described for the first time byLe Sage, which 
produces a green coloring-matter, while on the other it is referable 
to biliverdiu. When green stools occur frequently this condition 
is associated with the clinical symptoms of a severe cholera infantum. 

Quite characteristic also are the ipecacuanha stools, which closely 
resemble the so-called acholic stools. The green color produced by 
calomel, the yellow by santonin, rheum and senna, the black by iron, 
manganese and bismuth, have already been mentioned (see p. 161). 

Macroscopic Constituents. 

Alimentary Constituents. After having thus considered the 
number of stools, their consistence, reaction, odor, and color, it is now 
necessary to look for gross admixtures, and especially for the presence 
of undigested material, such as pieces of meat, flakes of casein — this 
especially in the stools of children — and even fragments of amyla- 
ceous food. The occurrence of such a condition, constituting what 
was formerly known as lientery, is always indicative of disturbed 
intestinal or gastric digestion, or both. It is, hence, observed in 
cases of chronic intestinal catarrh, febrile dyspepsia, following the 
use of cathartics, etc. 

Occasionally also a condition of affairs is seen in which almost un- 
altered food in large amounts is found in the feces, owing to a direct 
communication between the stomach and the colon, as in cases of 
perforating ulcer or carcinoma of the stomach. 

Mucus and Mucous Cylinders. As long as mucus occurs in 
small particles only adherent to otherwise normal feces it is of no 
pathologic significance. Larger amounts are almost always indicative 
of a catarrhal condition of the colon or rectum, no matter whether 
the stool be otherwise normal, or whether diarrhoea exist at the time. 
In acute intestinal catarrh, when the large intestine is likewise in- 
volved, large amounts are frequently observed. Peculiar forma- 
tions are occasionally seen, viz., so-called mucous cylinders, which 
are passed in large or small fragments in a condition which has been 

12 



278 CLINICAL DIAGNOSIS. 

described by Nothnagel as enteritis membranosa, or colica mucosa. 
Such masses, which at times measure a foot or more in length, 
are ribbon- or net-shaped and are usually passed in the absence of 
fecal matter with severe tenesmus. They closely resemble Cursch- 
niann's spirals, but lack the central thread and Charcot-Leyden crys- 
tals. They are probably indicative of chronic constipation associated 
with catarrh of the colon. Not to be confounded with this condition 
is the passage of masses of mucus which do not present the cylin- 
drical form, but which also may be passed with a great deal of tenes- 
mus and in the absence of fecal matter, in cases of nephroptosis, 
associated with gastroptosis and enteroptosis. These are, however, 
in all probability, also referable to a catarrhal condition of the colon. 
In cholera asiatica particles of mucus are seen which resemble 
grains of rice, the presence of which was formerly regarded as char- 
acteristic of this disease ; they occur, however, also in ordinary 
catarrhal conditions. 

Biliary and Intestinal Concretions. Most important from a 
diagnostic standpoint is the examination of the feces for the presence 
of biliary and intestinal concretions, which should never be neglected 
in cases of colicky abdominal pain of doubtful origin, whether asso- 
ciated with jaundice or not. 

When searching for gallstones the feces should be digested with 
water and passed through a fine sieve. Biliary concretions may then 
be found as small crumbling masses or as hard stones presenting an 
irregular contour, or the smooth characteristic facets. In size they 
may vary from that of a millet-seed to that of a pigeon's egg ; large 
stones are but rarely passed by the bowel, unless perforation has 
occurred into the intestines and usually into the colon. 

Some calculi consist almost entirely of cholesteriu, while others are 
composed essentially of inspissated bile, and still others of calcareous 
salts. The former are the most common and are readily recognized by 
their softness and color, which may be white, grayish, bluish, or 
greenish. Their specific gravity is lower than that of water. Very 
frequently they contain a nucleus, composed of earthy sulphates or 
phosphates. An analysis by the author of a large stone of this kind 
weighing 10.548 grammes, gave the following results : 

Cholesterin 72.59 per cent. 

Mineral salts 247 " 

Fats 5.09 

Biliary pigments 13.93 " 

Organic matter 7.27 " 



THE FECES. 179 

Calculi which consist largely of biliary pigments arc brown in 
color. They are hard and heavier than water. Frequently they 
contain traces of copper and zinc. (Fig. 41.) 

Fig. 41. 




2> 



Gallstones, 
a. Cholesterin ; b. Pigment-stones. 

Calculi composed of calcareous salts generally present an irregular, 
roughened contour. 

AVithin recent years Welch observed the presence of pure colonies 
of the bacterium coli commune in gallstones, apparently forming 
their nuclei. 

Analysis of Gallstones. The stone is finely powdered and 
dried at a temperature of 100° C. It is then extracted with boiling 
water, and the washings concentrated upon a water-bath to about 
100 c.c. One portion of this amount is evaporated to dryness, and 
the soluble residue, as well as the mineral ash, determined after desic- 
cation at a temperature of 105° C. The other portion is likewise 
evaporated to dryness and extracted with alcohol containing a small 
amount of ether, sodium glycocholate being thus obtained. After 
treatment with hot water, as described, the substance is successively 
extracted with alcohol and ether. In the alcoholic extract fats and 
a small amount of cholesterin will be found. The greater portion of 
the latter is contained in the ethereal extract. The residue, which is 
insoluble in hot water, alcohol, and ether, is treated with a moderately 
strong solution of hydrochloric acid, the earthy phosphates aud oxides 
being thus obtained united to pigments. The bilirubin is removed 
from the latter by extracting with boiling chloroform. The pig- 
ments which are not dissolved in this manner are biliprasin, bili- 
humin, etc. 

Intestinal concretions (enteroliths) are rare and usually come from 
the appendix. At times they contian some foreign body, such as a 
grape-seed, as a nucleus, upon which calcium and magnesium salts 
have become deposited. 



18 q JLINICAL DIAGNOSIS. 

Microscopic Examination. 

-ration should be directed especially to the presence of eggs of 
parasites, protozoa, certain pathogenic bacteria, remnants of food, 
blood-corpuscles, and pus. 

Technique. In hospital work the stool should be passed into a 
well-warnied bed-pan and examined at once. This is particularly im- 
portant in the search for amceba?. Iu private practice patients should 
be instructed to send their stools to the physician at once, when 
suspicious-looking particles should be placed upon the warm-stage, 
or examined upon a well-warmed slide. A very convenient form 
of warm-stage, which may he obtained from instrument-makers 
at low cost, is composed of brass and made to be held in position on 
the stage of the microscope by spring clips. It is about 8 cm. long 
and 3 cm. broad, and has cemented to a recessed bottom an ordk 
glass slip ; an opening of 1.35 cm. is in the centre of the stage. To 
one of the long sides of the brass stage is fitted a projecting stem, 
about 10 cm. long, to which the heat of a spirit-lamp is applied. 

For ordinary purposes it is well to place the stool, if watery, in 
a conical glass and to cover it with a layer of ether. If mushy 
or firm, it should be spread out upon a plate and covered with 
a layer of turpentine, or a 5 per cent, solution of carbolic acid or 
thymol. 

Remnants of food. It has already been pointed out that various 
microscopic remnants of food are observed in normal feces. In 
pathologic conditions it is necessary to determine whether or not such 
remnants be present in abnormal amount, presupposing, of cou: -t. 
that excessive quantities of food have not been ingested. It is 
often possible to draw definite conclusions as to the state of intes- 
tinal digestion from the excess of one form of non-digested material 
over another. The presence of large quantities of undissolved starch 
may be regarded as indicating a serious catarrhal condition of the 
small intestine. It may, indeed, be said that the occurrence of 
more than mere traces of this material should always be regarded 
with suspicion. An increase in the number of muscle-fibres will 
likewise be observed under the same conditions. The so-called 
acholic xtoote are very rich in fats, occurring mostly in crystalline 
form. Such stools are mosr commonly seen in cases of obstruc: ion 
of the biliary ducts, but may also occur when these are patent. 
WheD ass ted with jaundice the diagnosis of biliary obstruo::::: 



THE FECES. 181 

is usually justifiable. The author has repeatedly observed acholic 
stools in cases of duodenal catarrh in the absence of jaundice. Von 
Jaksch speaks of their occurrence in cases of intestinal tuberculosis, 
chronic nephritis, chlorosis, chronic tubercular peritonitis, and in 
intestinal indigestion of children. 

Nothnagel supposes the absence of normal color in cases in which 
the biliary ducts are undoubtedly patent to be referable to the presence 
of colorless decomposition-products of bilirubin or their chromogens, 
and it has been possible, as a matter of fact, to extract large quantities 
of urobilin from such feces with acidulated alcohol. 

Epithelium. Epithelial cells, when present in large numbers, 
always indicate an inflammatory condition of some portion of the 
intestinal tract. 

Red Blood-corpuscles. Unaltered red blood-corpuscles, accord- 
ing to Xothnagel, are but rarely observed in the feces no matter how 
intensely red they may be colored, provided that an ulcerative pro- 
cess affecting the colon or the rectum can be excluded, in which case 
large numbers may be observed, as, for example, in the severer 
forms of dysentery. If the hemorrhage has occurred higher up in 
the intestine, large and small masses of a brownish-red color are 
seen, which consist of hasmatoidin, instead of red blood-corpus- 
cles. These are mostly amorphous, but in the same or other 
specimens the characteristic rhombic crystals of hasmatoidin may be 
observed. In general it may be said that the higher the seat of the 
hemorrhage the darker will be the color of the pigment and the less 
the chances of finding well-defined red corpuscles. In such cases 
recourse must be had to the hsemin test (p. 37). 

Leucocytes. The presence of a large number of leucocytes usually 
indicates a severe catarrhal, if not an ulcerative, condition of the intes- 
tines, the number of leucocytes or pus-corpuscles standing in a direct 
relation to the intensity of the morbid process. Pure pus in large 
amounts is observed especially in dysentery and in cases in which 
accumulations of pus have perforated into the gut from adjacent 
organs or cavities. (See also p. 177.) 

Crystals. The crystals which may occur in the feces have already 
been briefly considered (p. 163). Of these the so-called Charcot- 
Leyden crystals deserve to be especially mentioned. While occurring 
at times in normal stools, as also in those of typhoid fever, dysen- 
tery, and phthisis, such observations are rare. They appear to be 
quite constantly present, on the other hand, in cases of anchylosto- 



182 CLINICAL DIAGNOSIS. 

niiasis and anguilluliasis. They are also frequently associated with 
ascaris lumbricoides, oxyuris, taenia solium and saginata. In cases 
of trichocephalus they are seen but rarely, while they are always 
absent in the case of taenia nana. These observations, made by 
Leichten stern, are very important, and, according to the same obser- 
ver, the occurrence of Charcot-Leyden crystals should always excite 
suspicion as to the existence of helminthiasis and lead to a careful 
examination of the feces for the ova of parasites. Their persist- 
ence in the feces after the evacuation of what would appear to 
be a complete taenia should be regarded as indicating the non- 
removal of the head. In a case of amoebic colitis, occurring in the 
practice of Dr. Lewis, of Baltimore, these crystals were also observed 
in fairly large numbers. Fat-crystals are found in very large 
numbers in the so-called acholic stools (p. 180). 

Animal Parasites. 

The animal parasites encountered in the feces may be divided into 
the following classes : 

I. — Protozoa : 

Rhizopocla, 

Monads ; amoeba coli. 
Sporozoa, 

Coccidia. 
Infusoria, 

Cercomonas intestinalis. 

Trichomonas intestinalis. 

Paramcecium coli. 

II. — Vermes : 

Platodes, 
Cestodes, 

Taenia mediocanellata. 

Taenia solium. 

Taenia nana. 

Taenia flavapunctata. 

Tapnia cucumerina. 

Bothriocephalus latus. 
Trematodes, 

Distoma hepaticum. 

Distoma lanceolatum. 

Distoma Ehatonisi. 



THE FECES. 183 

Annelides, 

Nematodes, 
Ascarides, 

Ascaris lumbricoides. 
Ascaris mystax. 
Oxyuris vermicularis. 
Strongyloides, 

Anchylostoma duodenale. 
Trichotrachelides, 

Trichocephalus dispar. 
Trichina spiralis. 
Rhabdonema strongyloides. 
Anguillula intestinalis. 
III. — Insecta : 

Piophila casei. 
Drosophila melanogastra. 
Honialomyia. 
Hyodrothoea meteorica. 
Cystoneura stabulans. 
Calliphora erythrocephala. 
Palleuria rudis. • 
Lucilia csesar. 
Lucilia regina. 
Sarcophaga hseniorrhoidalis. 
Sarcophaga haematoides. 
Eristalis arbustorum. 
Anthornyia. 

Protozoa. Up to the time of Losch in 1875 no one had sus- 
pected the protozoa occasionally found in the feces as being disease- 
producers ; their presence, especially the so-called monads, small 
granular pear-shaped bodies, ofteu provided with a flagellum, it is 
true, had been frequently observed previously, but no one ever 
ascribed any significance to these small animal organisms. Such 
monads have been observed in the feces of patients afflicted with 
various maladies, such as acute and chronic intestinal catarrh, 
typhoid fever, phthisis, cardiac disease, entero-colitis, and even in 
healthy sucklings and children. Although no definite connection 
has so far been established between pathologic conditions and these 
minute organisms, the possibility of such relation existing cannot, 
nevertheless, be altogether excluded, the number of observations 
upon the subject being as yet too small. 

Far more importaut is the parasite discovered by Losch in 1875, 
and termed by him the amoeba coll. The history of the discovery 
of this parasite and its relation to those severe forms of tropical 



184 CLLS'ICAL 1 

":r-abseess which are met with even in our more 
temperate zones, is of such interest, and at the same time illustrates 
so well the absolute necessity of the general practitioner being ac- 
quain: :he technique of microscopic work, that it may not be 

out of place to enter into this subject more fully. 

In 1875 Ldsch discovered, in the stools of dysenteric pat: - 
cell-like bodies of a roundish, pear-shape, oval or irregular form. 
ng about very actively. He did not regard these as the cause 
of the lisease, however, but looked upon them as being only acei- 
":!::.'>•- ;■:'— t n:. Siir.i'ar :: : r.es li li :I --en : - n H:::_ K;n^ 

Normand in cases of colitis ; and also by von Jaksch. Sansino 
found them in a case in Cairo, and Koch in East Indian dysentery. 
It is interesting to note that Koch was the first to suspect the exist- 
ence of a definite relation between dysentery and these organ:- ms. 
Cunningham claims to have found amoebae frequently in the stools of 
cholera patients at Calcutta, and Grassi in normal stools, but especially 
abundant in cases of chronic diarrh<:e: Whether all these observa- 
nce correct, and whether th ganisms observed were identical 
in all cases, is, of course, difficult to say. So much is certain that 
the subject was still a very unsettled one when Kartulis announced 
" that dysentery and tropical liver-abscess, associated with dysentery. 
are caused by the presence of the amoeba coli," basing his conclusion 
upon an examination of 500 cases. The fact that this parasite was 

sent in all other intestinal diseases, such as typhoid fever, intestinal 
tuberculosis, the ordinary forms of diarrhoea, etc., speaks most strongly 
in favor of Kartolis's view. 

In perfect accord with these observations were those made at the 
- H .::ns Hospital by Osier. Larleur. and Councilman. Osier 
was the first in this country to demonstrate the presence of the amceba 
coli in a case of lr - ss in the pns of the abscess an in 

- ^ _ . Musser, and Dock confirmed these observations, 
so that the pathogenic character of the amceba coli may now be re- 
garded as an established fact. This statement is based not only upon 
the few facts, more historical in character than otherwise, whi 

- een deta rather upon the ensemble of collected data. 

among which the absence of micro-org nisms other than the amoeba 
m th- the liver-abscesses, and the constant presence the 

latter in such cases, rank among the most important. 

of the am : ies from 10 a to 20//. When at rest their 

outline is circular, as a rule, occasionally ovoid; but when in motion 



THE FFA '/■>. 



185 



they present the extremely irregular contour of moving amoeboid 
bodies (Fig. 42). The protoplasm can be differentiated into a trans- 
lucent homogeneous ectosarc or mobile portion, and a granular endo- 
sarc, containing the nucleus, vacuoles, and granules. Within the 
endosarc the vacuoles constitute the most striking feature. Some- 
times the interior seems to be made up of a series of closely set clear 
vesicles of pretty uniform size. As a rule, one or'two larger vacu- 
oles are present, the edges of which are not infrequently surrounded 
by fine dark granules. True contractile vesicles displaying rhythmic 
pulsations have not been observed, although the vacuoles at times 
may be seen to undergo changes in size. In some the nucleus is 
quite distinct, while in others it may be altogether invisible. 



Fig. 42. 




The amoeba coli. 



Most distinctive are the movements of these bodies. From any 
part of the surface a rounded hemispherical knob will project, and 
with a somewhat rapid movement the process extends and the gran- 
ules in the interior flow toward it. In these movements the clear 
ectosarc seems to play the most important part. 

In this connection the author wishes to refer to the occurrence of 
Laveran's plasmodium malarice enclosed in red corpuscles, in the 
stools of cases of malarial colitis. In one case of chronic malarial 
intoxication with dysenteric symptoms the diagnosis was first made 
after an examination of the stools for amoeba?, which, however, were 
absent, while a number of plasmodia could be demonstrated, point- 
ing out the probable nature of the colitis. 



186 



CLINICAL DIAGNOSIS. 



Among the sporozoa the coccidia found from time to time in 
human stools are of interest. These are egg-shaped organisms, pro- 
vided with a thin shell, 0.022 mm. long, and containing in their inte- 
rior a large number of nuclei, usually arranged in groups. Such 
formations attack by preference the epithelial cells of the intestinal 
canal and gradually lead to their destruction ; of their pathogenic 
nature nothing is known. 

The infusoria mentioned before, i. e., the cercomonas intestinalis, 
trichomonas intestinalis, and paramoecium coli appear to be definitely 
associated with certain morbid conditions, in which diarrhoea is one 
of the most prominent symptoms. 

The cercomonas intestinalis is a pear-shaped organism, provided 
with a distinct nucleus and eight flagella. The head-portion of 
the body tapers obliquely and presents a depression (Fig. 43). As 



Fig. 43. 




Cercomonads from the stools. (Lajibl.) 

a, rnegastoma entericum (Grassi) ; b, encysted forms of cercomonas intestinalis ; 

c, cercomonas intestinalis after loss of its tentacles. 

this parasite seems to be always associated with diarrhoea, as in 
cholera, typhoid fever, etc., the impression is obtained that it can 
only thrive in an already diseased digestive tract, but is then 
able to cause continuous diarrhoeic discharges. According to Grassi 
and Schewiskoff, it possibly produces anaemia and diarrhoea in 
man in consequence of its action upon the epithelial cells of the 
intestines, the resorptive processes becoming thereby very much 
impeded. 

Trichomonas intestinalis is distinguished from the cercomonas by 
its greater size and the presence of a row of fine cilia upon the 
periphery of its body. 

Paramecium coli (balantidium coli) is egg-shaped, 0.1 mm. long, 
and covered with very fine cilia, which are grouped most densely 



THE FECES. 187 

about the mouth, while the anus is surrounded by but few. In its 
interior are found a nucleus and two contractile vesicles, frequently 
fat-droplets, starchy particles, etc. 

Other infusoria also occur in the feces in pathologic conditions, 
diarrhoea being always the most prominent symptom. 

Vermes. The class vermes has interested the physician since 
times immemorial, and is referred to in the writings of Hippocrates 
and others, special mention being made of the ascarides, called lum- 
brices, and the platodes, called lati. Speaking of the former, Lucas 
Tozzi in 1686 says, "They find their way into the heart and its 
pericardium, into the brain, the lungs, the veins, gall-bladder, aud 
urinary bladder, where they are difficult to catch." The same author, 
speaking of their effects upon the body, enumerates the following 
conditions as caused by their presence: epilepsy, vertigo, sopors, 
delirium, convulsions, headache, syncope, palpitations, feeling of 
anxiety, cough, vomiting, nausea, diarrhoea, hiccough, prickling, 
borborygmi, erosions, tabes, acute and chronic fevers, and innum- 
erable other maladies. 

It was then deemed very important to make a diagnosis before 
the administration of an anthelmintic, a point which it is well to bear 
in mind at the present day, and the eggs of the parasites should be 
sought for in every suspected case before the administration of drugs. 
When segments of tapeworms or ascarides are passed a skilled 
physician is not needed to tell the patient that he has worms, but 
a scientific physician is necessary to tell his patient that his ailments 
are due to worms, when these themselves have not as yet been observed 
in the stools. 

Taenia medio canellata (or saginata) (Fig. 44) is the taenia most 
common in this country, the taenia solium being its representative 
in Europe. It is from 4 to 8 m. in length, and its proglottides or 
segments are longer than those of taenia solium. The head is sur- 
rounded by four pigmented suckers, each being usually encircled by 
a black line. The length of the segments diminishes in all taeniae 
as the head is approached, but not quite so markedly as in the taenia 
solium. In an individual segment the very-much branched uterus, 
with its lateral opening, can readily be discerned. The eggs of 
taenia mediocanellata closely resemble those of taenia solium, but are 
more oval and covered by a vitelline membrane ; the absence of 
hooklets in the embryo aids in distinguishing them from those of 



188 



CLINICAL DIAGNOSIS. 



taenia solium. The cysticercus of taenia mediocanellata occurs iu 
cattle and has not as yet been observed in the human being. 



Fig. 44. 






Taenia saginata ; head; proglottis; egg. (Reichert's eye-piece III., objective IV.) 
(v. Jaksch.) 

Tcenia solium is from 2 to 3.5 m. long, its proglottides measuring 
from 9 to 10 mm. in length, by 6 to 7 mm. in breadth. The head 
(Fig. 45) appears as a black speck, about the size of a pin-head. 

Fig. 45. 




Head of T. solium. X 45. (Leuckaet.) 



The square form of the segments only appears about 1 m. back of the 
head, while the segments rapidly diminish in size as they approach 



Fig. 46. 





Ova of T. solium. (Leuckaet.) 
a. with yolk ; b, without yolk, as in mature segments. The hard, brown shell is indicated. 

the latter. The head itself is provided with four pigmented suckers, 
and a rostellum, furnished with about twenty-six hooklets. The 



THE FECES. 



189 



uterus of the individual segment has but few branches compared 

with that of the taenia mediooanellata. The eggs (Fig. 46) arc oval 
and surrounded with a thick striated membrane ; in their interior 
the hooklets of the embryos can usually be made out. 

At times, though rarely, an autoinfection with the proglottides of 
taenia solium has been observed in the human being. Under such 
conditions the embryos of the worm are set free in the stomach, and 
may then migrate into various parts of the body, where they become 
encysted, constituting the so-called cysticercus cellulosce stage in the 
development of the parasite. Most commonly the cysticerci are 
found in the skin ; they have, however, also been observed in the 
heart, the brain, and the eyes. The author had occasion to observe 
a case of this kiud at the Johns Hopkins Hospital (reported by 
Osier). The patient, a laboring-man, had never worked as a butcher 
or a cook, and never had a tapeworm. The cysticercus nodules, 
which were situated between the skin and the fascia, were very num- 
erous, seventy-five being counted on one day. One of these nodules 
was removed for examination and shown to be referable to the cysti- 
cercus of ta?nia solium. The only subjective complaints in this case 
were pains in the arms and legs. 

Fig. 47. 






Taenia nana. Head, with rostellum drawn in ; proglottis; egg. (v. Jaksch., 



Tcenia nana.] This parasite (Fig. 47) has not been observed in 
America, but seems to be the most common tapeworm in Italy 
and Egypt, being found especially in young people, and often 
causing severe nervous symptoms, such as convulsions, loss of con- 
sciousness, and even melancholia. It is only 10 to 15 mm. long, 
and 0.5 mm. broad ; its head is ball-shaped and provided with four 
suckers and a rostellum, bearing twenty-two to twenty-four hooklets 



190 CLINICAL DIAGNOSIS. 

on its anterior edge. The individual segments are very short, being 
about four times as broad as long. The uterus is oblong and con- 
tains numerous ova ; the membrane of the latter is not striated, but 
consists of a double layer, containing a spiral thread and granular 
material. In its interior the embryo may be observed, provided 
with five or six booklets. The number with which this parasite at 
times infests the digestive tract is often astonishing, amounting to 
4000, or even more. The mode of development of the parasite is 
unknown ; possibly the cysticercus stage occurs in snails, which are 
frequently eaten raw in Egypt and Italy. 

Tcenia flavapunctata was first described in man by Leidy and 
Porona. It measures from 12 to 20 mm. in length, and is armed 
with two suckers, but without a rostellum ; its eggs are said to 
resemble those of taenia solium. 

Tcenia cucumerina (Fig. 48) is usually observed in children, the 
infection probably occurring through dogs. It is from 18 to 25 cm. 
long ; the head is provided with about sixty hooklets, surrounding 
a rostellum in irregular rows ; when the latter is projected it appears 
as a club-shaped protuberance. The ripe segments have a reddish 
color and are very much longer than broad; the eggs contain embryos 
already armed with hooklets. 

JBothriocephalus latus (Figs. 49, 50). This worm is 5 to 8 m. long; 
its head is shaped like a bean and provided with centrally situated 
suckers. The ripe segments are almost square in form, with the 
genital apparatus opening in the median line. The eggs are oval, 
0.07 mm. long and 0.045 mm. broad, surrounded by a brown en- 
velope on which at the anterior end a little lid may be made out. 
Their contents consist of protoplasmic spherules, all of about the 
same size, which are lighter in color in the centre than at the 
periphery. This parasite appears to be associated with certain forms 
of pernicious anaemia. Infection is thought to take place through 
the ingestion of insufficiently smoked or boiled pike. 

The trematocles are very rarely observed in the feces. 

Distoma hepaticum (Fig. 51) is 28 mm. long and 12 mm. broad, 
being formed like a leaf. The head is provided with a sucker, and 
a second sucker may be found on its ventral surface ; between the 
two the genital opening is located, leading into the skein-shaped 
uterus. The eggs are oval, measuring 0.13 mm. in length and 
0.08 mm. in breadth, the anterior end of each being provided with a 
lid; their color is brown. 



THE FECES. 



J91 



Fig, 48. 



Fig. 49. 





:S'fi'" 'iC .«, 

Taenia cucumerina. Head; proglottis; magnified, 
(v. Jaksch.) 



Fig. 50. 




Bothriocephalus latus. Head. 
Fig. 51. 





Bothriocephalus latus. 
Fig. 52. 





Distoma hepaticum. (Leuckart.) Distoma lanceolatum (X 8) and eggs, (v. Jaksch.) 



192 



CLINICAL DIAGNOSIS. 



Distoma lanceolatum (Fig. 52) is 8 to 9 mm, long, 2 to 3.3 mm. 
broad, lancet-shaped, tapering toward the head-end, but otherwise 
closely resembles the distoma hepaticnm. The eggs are 0.04 mm. 
long, 0.03 mm. broad, and contain the already developed embryos. 

Both distomas rarely give rise to severe symptoms. 

Distoma Rhatonisi does not occur in America, and has but once 
been observed in man — in China. 

Yery common are the annelides, and among these the nematodes. 

Ascaris lumbricoides (Fig. 53) is the well-known cylindrically 
shaped worm so common in children and in the insane. The head 



Fig. 53. 




Ascaris lumbricoides. (v. Jaksch.) 
a, worm, half natural size ; b, head, slightly magnified ; c, egg. (Eye-piece I., objective 8 A, 

Reichert.) 

consists of three projections or lips, which are provided with suckers 
and fine teeth. The male measures about 215 mm., the female 
about 400 mm. in length. The tail-end of the male is rolled up on 
its ventral surface like a hook, and provided with papillae. The 
genital aperture of the female is situated directly behind the anterior 
third of the body. The eggs are yellowish-brown in color, almost 
round, and measure 0.06 mm. by 0.07 mm.; they are surrounded 
by an irregular albuminous envelope, which is covered by a tough 
sheli ; the contents are coarsely granular. 



77/ A' FECES. 



193 



Asearis lumbricoides occurs all over the world, and also attacks 
the pig and the ox. Its presence may occasion very severe nervous 
symptoms, but fortunately this is but rarely the case. 

Asearis mystax (Fig. 54) is smaller and thinner than asearis lum- 
bricoides, but otherwise very similar. The head is pointed and pro- 
vided with wing-like projections, which constitute the main point 
of difference between the two. The male measures 45 to 60 mm. 
in length, the female 110 to 120 mm. Its ova are round, larger 
than those of asearis lumbricoides, aud enclosed in a membrane, which 
is covered with numerous small depressions. 



Fig. 54. 



Fig. 55. 




Asearis mystax. (v. Jaksch.) 
a, male ; b, female ; c, head ; d, egg. 




Oxyuris vermicularis. (v. Jaksch.) 
a, head ; b, male ; c, female ; d, eggs. 



Oxyuris vermicularis (Fig. 55). The male is 4 mm., the female 
10 mm. long. At the head three lip-like projections with lateral 
cuticular thickenings may be seen ; the tail of the male is provided 
with six pairs of papilla?, and the female with two uteri. The eggs 
are 0.05 by 0.02 to 0.03 mm. in size and covered by a membrane, 
showing a double or triple contour ; in the interior, which is coarsely 
granular, the embryos are contained. 

The most annoying symptom produced by this worm, which 
lives in the lower portion of the rectum, is itching, which is most 
distressing at night, when the worm usually emerges from the anus. 
In doubtful cases of pruritus ani et vulvae an examination of the 
feces should be made for this parasite. 

13 



194 



CLINICAL DIAGNOSIS. 



To the strongyloides belongs one of the most dangerous of animal 
parasites, viz., the anchylostoma duodenale (Fig. 56) (strongylus 
duodenalis). It has been found in Italy, Germany, Switzerland, 
and Belgium, but not as yet in America. In every case of severe 
anaemia in which no definite cause can be assigned the feces should be 
examined for this parasite and its ova, more especially in patients 
who have been working in tunnels or in clay. The stools may pre- 
sent a perfectly normal appearance under such conditions, but at 
times diarrhoea and blood may be observed. 



Fig. 56. 




Anchylostoma duodenale. (v. Jaksch.") 

a, male, natural size ; b, female, natural size ; c, male, magnified ; d, female, magnified ; 

e, head i eye-piece II., objective C, Zeiss) ; /, eggs. 

The male is 8 to 12 mm. long, the female 10 to 18 mm.; the head, 
which tapers somewhat, is turned toward the back ; the mouth cap- 
sule is hollowed out and surrounded by four teeth ; the tail of the 
male forms a three-lobed bursa, while that of the female tapers 
conically ; the genital opening is behind the middle of the body. 
Its eggs have an oval form and a smooth surface, measuring 0.05 
to 0.06 by 0.03 to 0.01 mm. In their interior two or three segment- 
ing bodies are found, which rapidly develop outside of the human 
body, so that after twenty-four to forty-eight hours embryos may be 
found in the same feces in which the eggs w r ere observed, or fully 
developed ova may be found after allowing them to stand for only a 
few hours, 

Trichocephatus dispar (Fig. 57). This parasite is said to be con- 
cerned in the production of beri-beri. It is formed like a whip, the 



THE FECES. 



195 



Fig. 57. 



last-end being the head-end, while the tail-end is very much thicker. 
The male measures 46 mm. and the feinale 50 mm. in length. 
The eggs are brownish in color, measuring 0.05 by 0.06 mm. in 
size, and presenting a doubly contoured shell, with a depression at 
each end closed by a lid. The contents 
are coarsely granular. 

Trichina spiralis (Fig. 58) is rarely 
found in the feces. The male measures 
1.5 mm. in length, and is provided with 
four papilla? between the conical lips. The 
female is 3 mm. long. The uterus is situ- 
ated nearer the head than the ovary, which 
opens into it. Fertilization occurs in the 
intestinal canal. The eggs develop into 
embryos in the uterus, emerge from 
this, and penetrate the intestinal walls, 
whence they are carried by the blood- 
current to the muscles. Trichinosis is far 
less common in the United States than in 
Europe. 

Anguillula intestinalis is 2.25 mm. long 
and 04 mm. broad ; its mouth is three- 
cornered and bounded by three little lips. The genital aperture is 
located between the middle and posterior third of the body. Its 




Trichocephalus dispar. a, 
male, slightly magnified; b, 
female, slightly magnified ;'c, 
eggs (eye-piece II., objective" 8 
A, Reichert). (v. Jaksch.) 



Fig. 58. 




Trichina spiralis in muscle. The elongated shape of the cysts is due to the fact that these 
were near the insertion of the muscle into its tendon. In the lowest specimen the worm is 
dead and calcified. X 90. (Coats.) 



196 



CLINICAL DIAGNOSIS. 



eggs are similar to those of anchylostoma duodenale, but longer and 
more elliptical, with tapering poles ; they are never found in the feces, 
only the embryos occurring here. When sexually mature the para- 
site is called anguillula stercorals ; this again gives rise to embryos, 
which mav in tarn enter the intestinal canal. The anguillula ster- 



FlG. 59. 




Anguillula stercoralis. (Bizzozeeo.) 

coralis (Fig. 59) has a rounded body, which presents an indistinct 
cross-striation. Its head is like the top of a cane and provided with 
two lateral jaws, each of which is armed with two teeth. The male 
measures 0.08 mm., the female 1.22 mm. in length The pathologic 
significance of this parasite has not as yet been definitely ascertained, 
but from its resemblance to anchylostoma duodenale it has become 
important from a diagnostic point of view. 



PLATE VI. 



A >x Ml 

Spirillum of Asiatic Cholera. Impression cover-slip from a colony 
thirty-four hours old. (Abbott.) 



FIG. 2. 



\ 



m 



\ 



Bacillus of ..mil and Babes.) 




ITS +' 



Bacillus of Typhoid Ferer from a culture twenty -four hours old, 
on agar-agar. . tt 



THE FECES. 1 97 

Insecta. As the larva? oi' the various insects met with in the 
feces have so far been very little studied, they will not be consid- 
ered at this place, particularly as they do not appear to possess any 
points of cliuical importance. 

Vegetable Parasites. Among the pathogenic vegetable para- 
sites the bacillus of cholera, of typhoid fever, and of tuberculosis, 
as well as the bacilli of Booker, the bacterium coli commune, and the 
bacillus lactis aerogeues, deserve especial consideration. 

As early as 1848 certain " vibrios " were observed in abundance 
in the stools of cholera patients by Virchow, and in 1849 by Pou- 
chet, Britton, and Swayne, no importance, however, being attached 
to their presence at the time. 

The first really accurate and detailed studies of the organism 
found in cholera stools were made in 1883 by the members of the 
French and German expeditions to Eyypt, sent out by the respec- 
tive governments to investigate the true nature of the dreaded disease. 
The results of this work were first published by Koch in his report 
to the sanitary office in 1883, and in 1884 by Strauss, Roux, Nocard, 
and Thuillier. 

As a special stain for the bacillus of cholera, analogous to that 
employed in the demonstration of the tubercle bacillus, is as yet 
unknowu, the diagnosis must necessarily be based upon the ensemble 
of the biologic and morphologic characters of the bacillus, as follows: 

1. By examiniug a flake taken from the suspected specimen with- 
out auy further preparation. 

2. By staining a similar specimen with some basic aniline coloring- 
matter. 

3. By making plate-cultures on agar-agar and gelatin. 

4. Should comma-like bacilli be found, tubes must be inoculated. 

5. By examining a drop in suspension. 

The comma-bacillus is a slightly arched or even half-moon-shaped 
little rod, somewhat shorter than the tubercle-bacillus (Plate V., 
Fig. 1). Occasionally two are situated in such a manner that their 
arches are directed in opposite directions, the appearance of an S 
resulting. Such bacilli Koch discovered in the intestinal contents 
and feces, rarely in the vomited matter, in asiatic cholera only. In 
the stools they at times occur in such numbers as to constitute pure 
cultures. In plate-cultures kept at a temperature of 22° C. white 
colonies with serrated borders may be observed after twenty-four 
hours. The color of such a colony is slightly yellow or rose-red, its 



198 CLINICAL DIAGNOSIS. 

central portion gradually assuming a deeper tint, and finally becom- 
ing liquefied. Upon agar plates they form a grayish-yellow, irregular, 
slimy coating, but do not liquefy the culture-medium. In stab- 
cultures, after twenty-four hours, a whitish color may be observed 
along the line of the stab ; around this there is formed a funnel- 
shaped depression, which gradually increases in size and apparently 
contains a bubble of gas. The upper portion of the culture-medium 
will at the same time be observed to become liquefied, the lower 
portion remaining solid for days. In the suspended drop spiro- 
chseta-like spirals are observed at the margins, which often present 
as many as twenty distinct arches. 

Upon what may be termed specific reactions in the diagnosis of 
cholera asiatica no reliance can as yet be placed, and even the cholera- 
red reaction of Brieger, obtained by treating cultures of the bacillus 
with concentrated muriatic acid, does not rest upon a sufficiently firm 
basis to be of service in the clinical laboratory. 

Certain poisons of the class of ptomaines have been isolated from 
pure cultures of the comma-bacillus by Brieger, and Pouchet in 
France partly succeeded in finding the same in cholera-stools. 
These poisons possess an extreme degree of toxicity, as is apparent 
from the fact that pigs which had been fed by Pichard upon such 
feces died after fifteen minutes to two and one-half hours. 

Closely related to Koch's comma-bacillus and possibly bearing to 
cholera nostras the same relation that the former bears to cholera 
asiatica is the bacillus of Finkler and Prior, discovered in 1884 and 
1885 (Plate V., Fig. 2). This is, however, readily distinguished 
from the former by the following characteristics : It is larger and 
thicker than the comma-bacillus ; the colonies on gelatin plate-cultures 
show equally round and sharp-edged forms, which present a granu- 
lar appearance under a low or a medium power, and are usually of 
a brown color. The organism liquefies gelatin very rapidly, a pen- 
etrating, excessively fetid odor being developed at the same time. 
In stab-cultures the bacillus of cholera asiatica forms during its 
growth a funnel-shaped depression, while the bacillus of Finkler 
and Prior forms a stocking-like depression. Further work is still 
necessary in this direction, which may not be altogether unprofitable 
and may even yield most important results. 

The typhoid bacillus, discovered by Eberth in 1880 in the abdom- 
inal organs of patients dead with typhoid fever, is, unfortunately, 
not so readily recognized as the organisms just considered. The 



THE FECES. 109 

main difficulty lies in its differentiation from the bacterium coli 
commune, with which it has many points in common. 

Eisner has recently discovered a method, however, which will enable 
the general practitioner to make a definite diagnosis of typhoid fever 
within forty-eight hours. An aqueous extract of potato (oOO 
grammes pro liter) is treated with 10 per cent, of gelatin and boiled. 
The solution is then filtered and sterilized. When needed, a portion 
is placed in au Erlenmeyer's flask and treated with 1 per cent, of 
potassium iodide. The mixture is then inoculated with fecal mate- 
rial and the necessary plates prepared. Upon this medium only a 
few species of bacteria will grow, mostly the bacterium coli and 
the typhoid bacillus. After twenty-four hours the bacterium coli 
colonies are already mature, while the typhoid bacillus colonies can 
scarcely be made out with a low power. After forty-eight hours, 
however, the latter appear as small, highly refractive, extremely fine 
granular colonies, closely resembling drops of water, which can be 
readily distinguished from the large, much more granular, brownish 
colonies of the bacterium coli. This difference is brought out par- 
ticularly well if dilated plates have been prepared. 

Brieger, who has carefully repeated the experiments of Eisner, 
states that typhoid bacilli are found in abundance in the stools as 
long as fever exists, while with approaching convalescence they 
diminish in number and ultimately disappear. If, notwithstanding 
the absence of fever, bacilli are found in notable numbers during 
convalescence, the occurrence of a relapse may be anticipated. 
Further researches will be necessary in order to determine the exact 
period of time after recovery during which the bacilli still occur in 
the feces. 

In pure cultures the typhoid bacilli present the following features: 

They occur in the form of rods of almost one-third the size of a 
red blood-corpuscle, or in threads composed of several rods, joined 
end to end. (Plate V., Fig. 3.) The ends are rounded off ; their 
length is equivalent to about three times their breadth. On bouillon- 
peptone gelatin they grow very readily, and after twenty-four 
hours colonies begin to appear. When slightly magnified these 
present a faintly yellowish color ; macroscopically they are barely 
visible. When kept at a temperature of 37° C, the formation of 
spores may be observed, especially when grown on media colored by 
phloxin-red or benzopurpurine. The rods and threads present quite 
active movements ; they do not liquefy gelatin. 



g CLINICAL DIAGNOSIS. 

Tubercle-bacilli, when present in the feces, in which they may be 
demonstrated as described in the chapter on Sputum, are indicative 
of intestinal tuberculosis, providing they be observed upon repeated 
examination and there be clinical symptoms present pointing to the 
bowel as the seat of disease, as otherwise they may be referable to 
swallowed sputa. 

In this connection the green bacillus of Le Sage, discovered by 
him in a certain form of infantile diarrhoea, must be briefly re- 
ferred to, the stools, as has been mentioned, being of a grass-green 
color. The production of this pigment in cultures is one of the char- 
acteristics of the organism ; when injected into the intestines of 
animals it is said to produce diarrhoea and a catarrhal inflammation 
of the mucous membrane. 

Booker has described nine different bacilli occurring in cases of 
infantile diarrhcea. Seven of these closely resemble the bacterium coli 
commune. Bacillus ,- A" is a bacillus with rounded ends, measur- 
ing: from 3 u. to 4 « in length bv 0.7 u in breadth. It is motile and 
liquefying. Colonies on agar and potato present a dirty-brown 
color. It is found in the stools of cholera infantum. 

The bacterium coli commune, while constantly present in normal 
feces, is described at this place, as modern researches have shown 
that it may at times develop pathogenic properties. It has thus been 
found in the pus in cases of purulent perforating peritonitis, angio- 
choiitis, pyelonephritis, and. as indicated elsewhere, at times forming 
the nucleus of gallstones. It occurs in the form of delicate or coarse 
rods, measuring about 0.4 p in length, which manifest a certain degree 
of motility, due to the presence of one or two polar flagella. The 
organism is stained by the usual aniline dyes, and is decolorized by 
Gram's method. The colonies upon gelatin closely resemble those 
of the bacillus of typhoid fever, forming small whitish specks in the 
gelatin, and delicate Alms with serrated borders upon the same me- 
dium, which, moreover, is not liquefied. They also grow upon potato. 
As in the case of the typhoid-fever bacillus the nitroso-indol 
reaction p. 198) can be obtained when the organism is grown upon 
peptone-containing media. In solutions of glucose active fermenta- 
tion takes place. 

The bacterium facta aerogenes (Escherich) closely resembles the 
orgauism just described, and may also at times develop pathogenic 
properties. It was recently found by Heyse in a case of pneumaturia. 
It is seen quite constantly in the stools of sucklings, but may also 



THE FECES. 201 

be met with in those of adults. It occurs in the form of rather 
stout rods, which frequently lie in pairs, resembling diplococci. The 
organism is non-motile. Like the bacterium coli commune, it is decol- 
orized by Gram's method. In plate-cultures it forms dense white 
films ; in stab-cultures a chain of white colonies resembling beads is 
seen. In the latter, moreover, if the stab be closed, bubbles of gas 
will be seen to form which rapidly increase in number and size. Milk 
is coagulated in large lumps in twenty-four hours ; the formation of 
gas is, at the same time, much more intense than in the case of the 
bacterium coli commune. 



Chemistry of the Feces. 

According to Hoppe-Seyler, mucin forms the principal constituent 
of the feces, both under physiologic aud pathologic conditions, always 
indicating, when present in increased amount, an increased activity 
on the part of the intestinal mucosa. Small flakes of mucus are 
usually met with in catarrhal conditions of the small intestine, and 
are then intimately mixed with the feces, while larger pieces are 
generally observed in catarrhal conditions of the large intestine. 
In order to demonstrate chemically the presence of mucin in the 
feces they are digested with water and treated with an equal volume 
of milk of lime, allowing the mixture to stand for several hours, 
when it is filtered and the filtrate tested with acetic acid. In the 
presence of mucin a cloud develops upon the addition of the 
acid. 

Albumin is demonstrated in the feces by treating them repeatedly 
with water slightly acidified with acetic acid. The filtrate is then 
examined for albumin according to methods given elsewhere (see 
Urine). Under normal conditions these reactions prove negative. 
Pathologically, however, serum-albumin has been observed in cases 
of typhoid fever and chlorosis. 

Peptones are normally absent from the feces. They have been 
observed in typhoid fever, dysentery, tuberculous ulceration, puru- 
lent peritonitis with perforation into the gut, atrophic cirrhosis, and 
carcinoma of the liver. Acholic stools are also usually rich in pep- 
tones. 

The peptones are demonstrated in the following manner : The 
feces are digested with water, so as to form .a thin mush ; they are 
then boiled, filtered while hot, and the filtrate examined for albumin, 



202 CLINICAL DIAGNOSIS. 

so as to be sure that all of this has been removed. The mucin is 
removed by treating with acetate of lead, when the filtrate is exam- 
ined for peptones, as described in the chapter on Urine (which see). 

Among the carbohydrates starch, glucose, and certain gums may 
be found. In order to demonstrate these the feces are boiled with 
water, filtered, and evaporated to a small volume. This solution 
may now be tested with pheuylhydrazin or Trommer's reagent 
for the presence of glucose (see Urine), and with a solution of 
iodo-potassic iodide for starch (see Saliva, p. 134). The residue is 
extracted with alcohol and ether, as described under the heading of 
fatty acids, and then with water. The filtrate of the aqueous extract 
is concentrated, boiled with dilute sulphuric acid, and then over- 
saturated with sodium hydrate. This mixture is treated with sul- 
phate of copper and boiled in order to test for dextrin and gums. 

Bile-pigment, normally absent from the feces, occurs in large 
amounts in catarrhal conditions of the small intestine, and may be 
readily demonstrated by Gmelin's method, viz., a drop of the filtered 
liquid or a particle of highly colored fecal matter is brought into 
contact with a drop of fuming nitric acid, when the yellow color will 
be seen to pass through the various shades of the spectroscope, the 
green shade being the most characteristic. 

Whenever there is increased intestinal putrefaction the fatty acids, 
phenol, indol, and skatol will, of course, be found in increased 
amounts. 



THE PHYSIOLOGY OF DIARRHCEA AND 
CONSTIPATION. 

Before passing on to a consideration of the condition of the stools 
in the more important diseases of the intestinal tract, it may be well 
briefly to consider the most common causes of diarrhoea and consti- 
pation. 

Diarrhoea. 

Supposing normal peristalsis to result from the stimulation of the 
nervous mechanism situated in the intestinal walls— i. e., the plexuses 
of Meissner and Auerbach— by normal chyme, it is apparent that an 
increased peristalsis indicates either that the intestinal contents pos- 
sess more irritating properties, or that the irritability of the intestinal 
nervous mechanism is increased. 



THE FECES, 203 

Among such abnormal stimuli the following may be mentioned : 

1. Thermic stimuli. The effect of these may be said to increase or 
decrease peristalsis in the same proportion as the thermic stimulus 
differs from the normal temperature of the body. A cold injection 
thus acts more promptly than a warm one, and in many people a 
glass of cold water taken early in the morning, before breakfast, 
is often followed by vigorous peristalsis. 

2. Mechanical stimulation. As an example of this the loose 
stools may be mentioned which follow a very large meal. A large 
injection similarly acts more energetically than a small one. In such 
cases it is supposed that the increased peristalsis is referable to the 
stimulation of a larger number of nerve-endings at the same time. 

3. Chemical stimuli. These are certainly the most important and 
those which probably lie at the bottom of most cases of diarrhoea. 
Among these must be mentioned : 

a. Certain medicinal substances belonging to the class of laxatives, 
drastics, cathartics, etc., some of which manifest a selective action 
for the intestinal tract, as their injection into a vein or hypodermically 
will also cause an increase in the peristalsis. 

b. Poisons : All the drugs of the Pharmacopoeia, with few excep- 
tions, beloug to this class, as when given in poisonous doses diar- 
rhoea is produced. 

c. Poisons contained in tainted food. 

d. Poisons produced in the intestinal tract itself, referable to 
abnormally active fermentative and putrefactive processes. 

e. Certain poisons produced by specific microbes, such as those 
of typhoid fever, cholera, etc. 

4. Psychic stimuli. As an example of these the diarrhoea of the 
student before examinations may be mentioned. 

As indicated above, peristalsis will also be increased when the 
nerve-endings in the intestinal mucosa are in a condition of increased 
irritability. This will naturally always be the case in any inflam- 
matory conditiou of the intestine, the abnormally filled bloodves- 
sels, and at the same time an altered condition of the transudate, 
causing stimulation of the fine nerve-endings. In acute ulcerative 
conditions this state is, of course, met with in its most marked form, 
while in chronic ulcerations, where there is a gradual death of nerve- 
aud muscle-substance, increased peristalsis is not so often observed, 
the stools, as regards consistence and number, scarcely differing from 
the normal. 



904 CLINICAL DIAGNOSIS. 

It mav thus be said that whenever intestinal peristalsis through 
one of these causes has become abuormally active diarrhoea must 
result, manifested by the passage of an increased number of stools, 
which are at the same time abnormally rich in water. The increase 
in the amount of water may be due to one or two causes : first, to 
increased ingestion, and, second, to diminished absorption. The first 
of these, however, can hardly ever be said to cause diarrhoea, and 
the latter will not result as long as resorption is undisturbed. 

The liquid stools following the administration of salts can probably 
be explained by assuming a retention of water in the alimentary 
canal, referable to their presence. By far the most frequent cause 
of watery stools, however, following the administration of a drug 
is an abnormally active peristalsis. 

Whether in pathologic conditions associated with the destruc- 
tion of epithelium the abnormal quantity of water observed in the 
stools can be ascribed to diminished absorption is a question which 
is difficult to answer, since inflammatory and ulcerative processes 
which, as has been seen, are* in themselves sufficient to produce in- 
creased peristalsis, and hence watery stools, are taking place at the 
same time. 

On the other hand, it appears highly probable that the frequent 
and persistent diarrhoea which occurs so constantly in cases of amy- 
loid degeneration is due to passive hyperemia in consequence of 
the degenerative changes taking place in the bloodvessel walls, re- 
sorption being thereby impeded. 

Remembering at the same time that the resorptive processes in the 
large intestine determine the form in which the intestinal contents 
leave the body, it is readily understood that increased peristalsis of 
this portion of the gut is the deciding factor in the production of 
diarrhoea, and without it an increased peristalsis alone, confined to 
the small intestine, would hardly ever be capable of causing this 
result. It follows also that the more the peristalsis of the entire 
alimentary tract is increased, the more will the feces assume the 
character of the contents of the small intestine. 

Constipation. 

Hitherto the effects of increased peristalsis upon the number and 
consistence of the stools have been considered. If now peristalsis 
becomes diminished, the opposite condition — I <?., constipation — will 
result, and iuversely, as in diarrhoea, this may be due to a dimin- 



THE FECES. 205 

ished irritability on the part of the nervous mechanism of the intes- 
tinal walls. This is especially the ease in the condition generally 
designated as " habitual constipation," the degree oi' which will de- 
pend upon the part that the small and large intestines separately or 
together play in the process. In such cases, however, resorption 
is not increased in proportion, as might at first thought be imagined, 
and it appears to be a fairly well-established fact that for the carrying 
on of an efficient degree of resorption a certain degree of peristalsis 
is necessary. This is most beautifully exemplified in cases of cholera 
sicca, in which constipation exists although the intestines are filled 
with liquid. Whether central influences play a part in some of the 
cases must as yet remain an open question. 

Different from this condition are those cases of constipation which 
are not referable to a diminished peristaltic energy, but in which, 
instead of successive contractions and relaxations, a tonic contraction of 
the intestinal walls occurs. In some cases this is probably of central 
origin, as in basilar meningitis, while in others, as in lead colic, it 
may be secondary to a primary vaso-constriction along the intestines. 
It differs from ordinary constipation in the fact that everything that 
can be absorbed is here taken up. 

In the case of atony on the part of the intestinal muscles, finally, 
constipation will also result. This occurs, for example, after the use 
of cathartics, in peritonitis (in consequence of prolonged circulatory 
disturbances), and in drinkers the subjects of fatty degeneration of 
the muscular w 7 alls of the intestines. 



THE FECES IN VARIOUS DISEASES OP THE 
INTESTINAL TRACT. 

Acute Intestinal Catarrh. This condition follows the ingestion 
of excessive quantities of ordinary food, tainted food (meat, fish, beer, 
cheese, etc.), certain poisons, such as acids, alkalies, arsenic, corrosive 
sublimate, etc., when taken in toxic quantities. It is observed, fur- 
thermore, as the result of a general infection, as in summer diarrhoea, 
cholera nostras, typhoid fever, severe malaria, and is also associated 
with disturbed circulatory conditions, producing a passive hyperemia 
of the gastro-intestinal mucosa, as in various diseases of the liver 
and portal system, in chronic heart and lung diseases, etc. How 
far these circulatory disturbances may be considered as primary causes 
remains to be seen. Possibly they merely act as predisposing 



206 CLINICAL DIAGNOSIS. 

causes of certain chemical processes taking place in the intestinal 
contents. 

The stools in these cases are usually increased in number in pro- 
portion to the degree in which the large intestine is aSected. Two 
or three, or ten or more, stools may be passed within the twenty- 
four hours. In consistence they are mushy aud even watery, the 
percentage of water in some cases rising to 90 or 95 per cent. 
Their color is usually light-yellow, but may, at times, be green, 
Microscopically, remnants of food may be found in large quantities, 
as also numerous bacteria, triple phosphates, isolated pus-corpuscles, 
and desquamated cylindrical epithelial cells. 

A duodenal catarrh can only be diagnosed when associated with 
icterus. 

tarrh of the jejunum and ileum, when the large intestine is not 
aSected : The stools here are firm, formed, but speckled with small 
hyaline particles of mucus, visible only with the microscope. Usually, 
however, the large intestine is also aSected when the stools are loose 
and contain undigested particles of food, the latter indicating mischief 
in the small intestine. Bile-pigment is also met with, as only the 
contents of the small intestine give Gmelin's reaction. 

Catarrh of the large intestine : This is probably always present 
whenever diarrhcea exis:~. 

A^ hen the colon is extensively aSected mucus appears in larger 
masses than otherwise, and if the catarrh is very low down the feces 
mav be formed, but are covered with mucus. 



Fig. 60. 






- discharge from a case of enteritis membranosa. 

Chronic Intestinal Catarrh. This may follow an acute attack, 
and may also occur after dysentery, severe malaria, typhoid fever. 
etc. Diarrhoea usually alternates with constipation. It is rare in 



THE FECES. 207 



adults, while in children it is quite frequently observed. Macro- 
scopically and microscopically the same picture is seen as in the acute 
form. 

Enteritis membranosa is one form of chronic intestinal catarrh and 
characterized essentially by the evacuation of cylindrical masses of 
mucus, as described on p. 178. (Fig. 60.) 

Cholera Nostras. This is an infectious disease affecting both 
stomach and intestines, being probably dependent upon the presence 
of the bacillus of Finkler and Prior. 

The stools are at first feculent, but soon become more and more 
colorless and watery, until they may ultimately resemble the so-called 
rice-water stools of cholera asiatica, containing much serum-albumin 
and mucin. 

Intestinal Catarrh of Infants. The normal stools of infants, 
up to the time of weaning, are of an egg-yellow color ; they are 
mushy, uniform, and of a faintly acid odor. In this disease six or 
seven stools are daily passed, which are more liquid than normally, 
of a fetid odor, and containing flakes of casein. They are often 
green when passed, or may asume that color on standing. Mucus is 
present, and when the colon is especially affected may occur in 
tapioca-like particles. In severe forms pus-corpuscles, epithelial cells, 
and also small amounts of blood may be present. 

Dysentery. This is an infectious disease, probably caused by a 
bacillus discovered by Chantemesse and Widal. The stools during 
the first few days are irregular. A moderate diarrhoea then sets in, 
the stools being thin, but still feculent, numbering five or six per 
diem. After several days the diarrhoea increases and the stools now 
assume a definite character, numbering from ten to twenty, or even 
fifty or sixty in the twenty-four hours. At the same time they be- 
come scanty in amount, usually not exceeding 10 to 15 grammes at 
a time. They are now sero-sanguinous in character, and in them 
may oe found smaller or larger pieces of necrotic tissue. Microscop- 
ically blood-corpuscles, particles of mucus, pus-corpuscles, and num- 
erous bacteria are seen. According to the preponderance of blood, 
pus, mucus, etc., the stools are termed sanguinous, sero-sanguinous, 
puriform, or mucoid, etc. Shreds of mucus, resembling frogs' eggs 
or kernels of tapioca, which are, in all probability, casts of follicles, 
are also found. Typical dysenteric stools do not, as a rule, emit a 
marked odor, but in the gangrenous form they are very offensive. 

Amoebic Dysentery. This form of dysentery is especially inter- 



208 CLINICAL DIAGNOSIS. 

esting, not so much on account of its prevalence, however, as of the 
importance attaching to an early diagnosis, a successful treatment 
being altogether dependent thereupon, and differing entirely from that 
emploved in the more usual forms. 

The number of stools may vary within very wide limits — i.e., from 
six to twenty, or even thirty a day. They may be entirely mucoid, 
streaked here and there with pus and presenting a few grayish threads. 
Others seem to be made up of a greenish pultaceous mass, in which 
at times large greenish, irregular sloughs are observed. Such mu- 
cous stools are usually slight in amount. Occasionally large brown- 
ish, liquid evacuations are seen, in which small grayish-white masses 
occur, imbedded in blood-stained mucus. These latter contain the 
diagnostic amoebae most abundantly. 

For a satisfactory examination of such stools the bed-pan ought 
to be well warmed and brought to the laboratory immediately for 
examination. If this be impracticable, some of the material may be 
carried home in a suitable receptacle, when the above-mentioned 
small, grayish-white masses are best deposited upon a warmed slide, if 
a warm-stage be not at hand. One preparation after another must 
now be carefully looked over for actively moving amoebae, or, at 
least, for amoeba-like bodies which exhibit definite movements. (For 
a description of these parasites, see p. 183.) 

In addition to the amoebae other forms of animal parasites may 
here be met with, such as the trichomonas intestinalis, which may 
at times be present in very large numbers. 

Red blood-corpuscles in greater or less abundance, numerous pus- 
corpuscles, more or less degenerated cylindrical epithelial cells, bac- 
teria of all kinds, and even large pieces of necrotic tissue may further 
be found. 

Cholera Asiatica. The stools here are very numerous, being at 
first feculent, but soon becoming rice-water-like. As large a quan- 
tity as 200 grammes may be passed at each time. They are color- 
less, almost odorless, watery, and on standing a finely granular, gray- 
ish-white sediment may be seen to form at the bottom. The reaction 
is neutral or alkaline. They contain only 0.5 per cent, of solids, a 
little serum-albumin, and a large amount of sodium chloride. In 
severe cases blood may be present in variable amount. Microscop- 
ically, epithelial cells, triple phosphate crystals, and numerous micro- 
organisms are found. Among the latter the comma-bacillus is, 
of course, the most important (see p. 197). 









THE FECES, 



209 



Typhoid Fever. Typhoid stools are usually described as resem- 
bling pea-soup both in consistence and color. Their odor is, 
as a rule, highly offensive and characteristic, so much so, in fact, 
that the diagnosis of typhoid fever may at times almost be made 
from the odor of the stools. They contain a large amount of biliary 
coloring-matter; their reaction is always alkaline. Microscopically 
many bile-stained epithelial cells, some leucocytes, many triple phos- 
phate crystals, and an enormous number of micro-organisms, es- 
pecially the Clostridium butyricum of Nothnagel and Eberth's bacillus, 
are found. Later on they may assume the appearance of ulcera- 
tive stools and become almost black, owing to the presence of blood. 



MECONIUM. 

By mecouium are meant those masses which are first excreted by the 
bowel after birth. They are a thick, tenacious, greenish-brown mate- 
rial which has accumulated during the intrauterine life of the infant. 
Microscopically a few cylindrical epithelial cells, a few fat- droplets, 
numerous cholesterin- crystals, bilirubin-crystals, and lanugo-hairs are 
found. Micro-organisms aud their spores are absent, but soon after 
suckling has commenced thick, curved rods, measuring from 1 fi to 5 fi 
in length by 0.3// to 0.4// in breadth (Escherich), are found, as also 
a bacillus resembling the one causing lactic-acid fermentation. 

Chemically meconium contain bilirubin in considerable amount,, 
recognizable by Gmelin's reactiou, biliary acids, some fatty acids, 
chlorides, sulphates, phosphates of the alkalies and their earths. It 
does not contain urobilin, glycogen, peptones, lactic acid, tyrosiu, 
or leucin. 

An idea may be formed of its quantitative composition from the 
table of Zweifel, here appended, the figures given referring to 100' 
parts : 



Water . 
Solids 

Mineral matter 
Cholesterin . 
Fats 



79.8-80.5 per cent. 
20.2-19.5 

0.978 
0.797 
0.772 



14 



CHAPTER V. 

THE NASAL SECRETION. 

In the nasal secretion, which normally is small in amount, trans- 
parent, colorless, odorless, tenacious, and of a slightly saline taste, 
pavement-epithelium cells in large numbers, as well as some leuco- 
cytes and an enormous number of micro- 
FlG - 61 - organisms, are found (Fig. 61). Its re- 

action is alkaline. 

In acute coryza the amount is at first 
diminished, but soon after a very copious 
secretion occurs, w r hich is rich in epi- 
thelial cells and micro-organisms. When 
complicated with an ulcerative condition 
pus is observed in considerable amount. 

Occasionally, in cases of traumatism, 

cerebral tumors, etc., cerebro-spinal fluid 

Nasal secretion. is discharged through the nose, which may 

be recognized by the fact that it is free 

from albumin and contains a substance which reduces Fehling's 

solution. 

Of pathogenic organisms the tubercle-bacillus and the bacillus of 
glanders may occur in ulcerative disease of the nose, their presence 
indicating the existence of the corresponding affection. In ozsena 
a large diplococcus has been described by Lowenberg, which is said 
to be characteristic of the disease. Oidium albicans has been ob- 
served in rare cases. The same may be said of the occurrence of 
ascarides and other entozoa, which at times find their way into the 
nose. Charcot-Leyden crystals (which see) have been observed in 
the nasal discharge in cases of true bronchial asthma. 




CHAPTER VI 



THE SPUTUM. 



Definition. 



Without entering into the physiology of the act of coughing, it 
may be stated in a general way that cough is the first and most essen- 
tial factor in the elimination of irritating matter derived from the 
respiratory passages; i. e., the alveoli of the lungs, the bronchi, tra- 
chea, larynx, pharynx, aud posterior nares. The material which is 
thus removed is spoken of as expectoration or sputum, the study of 
which forms one of the most important chapters iu clinical diagnosis. 

General Technique. 

The sputum should be collected in suitable receptacles, constructed 
in such a manuer as to permit of their complete and easy disinfec- 
tion. The paper spit-cups (Fig. 62) which have been introduced 
within late years are admirably adapted to this purpose, as they may 
be destroyed immediately after use. 



Fig. 62. 





Sanitary spit-cup. 



When working with sputa which are known or suspected to be of 
tubercular origin the greatest care should be exercised to keep the 
expectoration from drying and becoming disseminated in the air, 



212 CLINICAL DIAGNOSIS 

Negligence in this respect may result in the most serious conse- 
quences. 

The macroscopic examination of sputa is most conveniently carried 
out by placing small portions of the material upon a plate of ordi- 
nary window-glass, of suitable size, which has been painted black 
upon its lower surface, and covering the same with a second and 
smaller plate. If it is desired to examine individual constituents 
which have been discovered in this manner, the upper plate is slid 
off until the particle in question is uncovered, when it may be re- 
moved to a microscopic slide and examined under a higher power. 

It is also very convenient to have a portion of the laboratory 
table painted black, when unstained plates of glass may be utilized. 
If these measure about 15 by 15 cm. and 10 by 10 cm., respectively, 
fairly large quantities of sputum may be examined in situ with a low 
power. 

General Characteristics of the Sputa. 

The Amount. The amount of sputum expectorated in the twenty- 
four hours varies within very wide limits, depending largely upon 
the nature of the disease. Thus only a few c.c. may be eliminated, 
or an amount reaching 600 to 1000 c.c. , or even more. Very large 
amounts are expectorated in cases of pulmonary hemorrhage and 
oedema of the lungs, also following the perforation of accumulations 
of pus derived from the thoracic or abdominal cavities into the 
respiratory passages ; furthermore, in cases in which large vomicse of 
tubercular or gangrenous origin exist, and finally in cases of abscess 
of the lung, bronchiectasis, and even in simple bronchial blennorrhoea. 
On the other hand, the amount may be very small, as in incipient 
phthisis, acute bronchitis, and iu the first and second stages of 
pneumonia. 

In private practice, as well as in hospital work, an idea should 
always be formed of the amount of sputum expectorated in the twenty- 
four hours, especially in cases in which this is abundant. It is apparent 
that a copious and long-continued expectoration cannot go on without 
exerting very detrimental effects upon the patient's general nutrition ; 
in cases of pulmonary phthisis, for example, Eenk has show that 3.8 
per cent, of all nitrogen eliminated in such cases is removed in this 
manner. Lanz in his recent experiments even found 5 per cent. 



THE SPUTUM. 213 

Consistence. The consistence of the sputum corresponds, in 
a general way at least, with its amount, and may vary from a 
liquid to a highly tenacious state. The cause of the tenacity of the 
sputum is but imperfectly understood. The mucin present does not 
appear to be the most important factor, as this lias been observed to 
occur in diminished amount in pneumonic sputa, which are noted for 
their high degree of tenacity. Kossel has suggested that this phenom- 
enon may be due to the presence of nuclein or nuclein derivatives, 
while others again refer it to the presence of abnormal albuminous 
bodies of unknown character. However this may be, sputa are at 
times and not at all infrequently seen where it is possible to invert 
the cup without losing a drop of its contents. This is observed 
especially in cases of acute croupous pneumonia up to the time of 
the crisis, providing that a catarrh of the bronchi does not exist at 
the same time. It is noted, furthermore, in cases of acute bronchial 
asthma, immediately after an attack, and also in the initial stage of 
acute bronchitis. 

In cases of oedema of the lungs, on the other hand, the sputa are 
liquid and present the general characteristics of blood-serum, being 
covered like all albuminous liquids, when brought into contact with 
the air, by a frothy surface-layer. Perfectly fluid are the sputa con- 
sisting of pure pus, observed in cases of acute pulmonary gangrene, 
pulmonary abscess, putrid bronchitis, and following the perforation 
into the lungs of an empyema or an accumulation of pus situated 
beneath the diaphragm. 

Color. The color of the sputa may vary greatly. They may be 
perfectly clear and transparent, gray, yellow, green, red, brown, or 
even black. Purely mucoid expectoration is almost transparent and 
colorless, as is also the* sputum of pulmonary oedema when not mixed 
with blood or pus. 

The larger the number of leucocytes the more opaque does the 
sputum become, assuming at first a white, then a yellow, and finally 
a greenish color, the two latter colors being usually indicative of the 
presence of pus. Green sputa, however, may also be observed when 
in some manner bile-pigment has become admixed with the sputa, as 
in cases of perforation of a liver-abscess into the lung, for example. 
Green-colored sputa may further be observed in cases of jaundice, 
and especially in pneumonia when accompanied by icterus. In 
cases of amoebic liver-abscess with perforation into the lung the 



214 CLINICAL DIAGNOSIS. 

sputa present a color resembling anchovy sauce, which is very char- 
acteristic. In one case the author recognized the nature of the dis- 
ease by simple inspection of the sputa. 1 

The inhalation of particles of carbon colors the sputum a grayish 
or even a black color ; the same or an ochre-yellow or red color is 
observed in cases of siderosis. 

A red color is usually indicative of the presence of blood, the 
intensity of the shade depending upon the character of the disease. 
It is seen especially after the formation of cavities in caseous pneu- 
monia, in incipient phthisis, heart disease, etc. In general it may be 
said that a clear, bright-red color indicates an arterial, a dark-red or 
bluish-red a venous origin of the hemorrhage. The exact shade will 
depend upon the length of time that the blood, no matter what its 
origin may be, has remained in the lungs. In pulmonary gangrene 
a dirty brownish-red color is observed, owing to the presence of 
methsemoglobin, aud, to some extent also, of hsematin. Quite char- 
acteristic is a chocolate-color, which is observed when a croupous 
pneumonia terminates in necrosis and gangrene. Equally character- 
istic is the rusty and prune-colored expectoration seen in cases of 
pneumonia, Occasionally a breadcrust-brown color of the sputa is 
observed in cases of gangrene and abscess of the lung, which is 
said to be quite characteristic, the color being due to the presence of 
hsematoidin or bilirubin. 

Rust-colored, punctate, or striped sputa, moreover, are said to be 
diagnostic of brown induration of the lung. 

Odor. Most sputa have no odor at all. Under certain condi- 
tions, however, the odor may be very marked : In cases of pulmonary 
gangrene or putrid bronchitis the odor is of a kind never to 
be forgotten, the stench, indeed, being frightful. A somewhat sim- 
ilar, slightly sweetish odor is observed in certain cases in which 
putrefactive organisms have entered the lungs and there exerted 
their action upon the accumulated sputa, in the absence of gangrene, 
as in cases of bronchiectasis, perforating empyema, and where ulcer- 
ative processes are taking place in the lungs, whether these be of 
tubercular origin or not. An odor like that of old cheese is occa- 
sionally observed in cases of perforating empyema, and tyrosin is, 
under such conditions, usually found. This body, however, has 
nothing to do with the odor of such sputa, both factors being merely 

1 See Johns Hopkins Hospital Bulletin, November, 1890. 



THE SPUTUM. 

indicative of certain putrefactive changes going on in the lungs. 
According to Leyden, the occurrence of tyrosin in sputa is usually 
indicative of the perforation of an old accumulation of pus into the 
lungs. 

Specific Gravity. The specific gravity of sputa varies within 
wide limits, mucous sputa having a specific gravity of 1.004: to 1.008, 
purulent sputa one of 1.015 to 1.026, and serous sputa one of 1.037 
or more. The determination of the specific gravity, however, will 
scarcely ever be of value in diagnosis. 

Configuration of Sputa. As a general rule the following forms 

of sputa, which may be termed pure sputa, present a homogeneous 

appearance : 

Mucoid sputa, -\ 

Purulent sputa, ! 

a , f Homogeneous sputa, 

berous sputa, ° ^ ' 

Sanguinous sputa, J 

with one exception, perhaps — the typically rusty sputa of croupous 

pneumonia ; while mixtures of any two or three of these may be 

classed as heterogeneous sputa : 

Muco-purulent sputa, ~\ 

Muco-serous sputa, [ 

. r Heterogeneous sputa. 

bero-sanguinous sputa, [ ° ^ 

Sauguiuo-muco-purulent sputa, J 

The so-called sputum crudum of the first stage of acute bronchitis 
may be regarded as an example of a purely mucoid sputum. A 
purely purulent sputum is usually indicative of one of the follow- 
ing conditions, viz., the perforation of au empyema or any other 
accumulation of pus into the lungs or bronchi, pulmonary abscess, or 
bronchial blennorrhcea. A purely serous sputum is found in cases of 
pulmonary oedema, and a purely hemorrhagic sputum in cases of 
severe pulmonary hemorrhage. 

Of the heterogeueous sputa, the most important are the so-called 
nummular sputa of phthisis in the second and third stages. These 
are characterized by the fact that when thrown or expectorated 
into water they sink to the bottom aud there form more or less 
roundish coin-like disks, from which property they have received 
their name. Such sputa are muco-purulent in character, and contain 
imbedded in a more or less homogeneous mass of mucus a focus of 
almost pure pus. Quite different from these are the so-called sputa 
globosa of the ancients, which consist of fairly dense, roundish, 



216 CLINICAL DIAGNOSIS. 

gravisb-white masses, secreted in old cavities wbicb have become 
lined with a granulation-membrane. 

Very important is tbe presence of small cheesy particles, which 
are occasionally found at the bottom of the spit-cup. They vary 
in size from that of a millet-seed to that of a pea, and are observed 
especially in the second and third stages of phthisis. Usually 
they contain tubercle-bacilli in large numbers, and frequently also 
elastic tissue. 

Not to be confounded with these, however, are certain small case- 
ous masses which are at times expectorated by perfectly normal in- 
dividuals, and also by patients suffering from acute tonsillitis, ozsena, 
etc., and which probably come from the tonsils or mucous cysts. 
These were formerly regarded as tubercles, and in hypochondriac 
individuals their expectoration may cause unnecessary anxiety. 
They are quite readily distinguished from the true caseous masses 
expectorated by phthisical individuals by the following charac- 
teristics : As a rule, they are expectorated unaccompanied by 
any admixture of pus, or even of mucus; rubbed between the 
fingers they emit an extremely offensive odor, which is referable to 
the presence of fatty acids ; an examination for tubercle-bacilli, 
moreover, will prove entirely negative. Quite characteristic, 
furthermore, is the peculiar, finely flocculent, granular appear- 
ance of the sputa seen after the perforation of an empyema into 
the lungs through a small aperture, which is not followed by 
pneumothorax. 

Occasionally, as in putrid bronchitis and gangrene of the lungs, and 
also in chronic bronchitis, ultimately leading to the formation of 
bronchiectatic cavities, an exquisite sedimentation is observed. Such 
sputa, when collected in a conical glass, usually present three distinct 
zones, the one at the bottom containing the cellular elements of the 
sputum, the second the pus-serum, and the third or superficial layer 
consisting of mucus and containing many air-bubbles. 

Macroscopic Constituents of Sputum. 

Elastic Tissue. Of macroscopic constituents which may be ob- 
served in sputa there may be mentioned, first of all, the occurrence 
of threads of elastic tissue and pulmonary parenchyma, which are 
seen in cases of phthisis, pulmonary abscess and gangrene. As their 
ultimate recognition, however, largely depends upon a microscopic 
examination, this subject will be considered later on. 



THE SPUTUM. 217 

Fibrinous Casts. Fibrinous easts are observed especially in 
cases oi' croupous pneumonia (Fig. 63) immediately before or after 
resolution lias taken place. They are also seen in cases of so-called 
fibrinous bronchitis (Fig. 64), and last, but not least, in cases of 
diphtheria, as in the latter disease the fibrinous exudation may not 
only attack the walls of the larynx and trachea, but may even ex- 
tend into the bronchi and their finest ramifications. Such fragments 
may vary in size from 12 cm. in length by several mm. in thickness 
to small fragments which only measure from 0.5 to 3 cm. in length. 

Fig. 63. 




Fibrinous coagulura from a case of croupous pneumonia. (Bizzozero.) 

The -fibrinous casts observed in cases of pneumonia, usually from the 
third to the seventh day, are of the latter size or even smaller, being 
derived from the ultimate twigs of the finest bronchioles. Those 
found in the rather rare disease, fibrinous bronchitis, stand between 
these two in size, being casts of the smaller and medium-sized bronchi. 
Attention is usually attracted to the presence of such casts by their 
white color ; often, however, they are yellowish-brown or reddish- 
yellow, owing to the presence of blood coloring-matter which has 
become deposited upon the casts, while at other times they are envel- 



218 



CLINICAL DIAGNOSIS. 



oped in mucus, when their recognition may become quite difficult. 
Such casts, when examined more carefully, will be seen to branch 
dichotomously, and to contain a cavity in their larger portion, while 
the finer branches appear to be solid. Microscopically they may be 
shown to consist of a large number of longitudinal and often net-like 
arranged fibres, containing blood-corpuscles and epithelial cells in 
their meshes. When treated with Weigert's fibrin-stain they are 
beautifully resolved. Charcot- Leyden crystals have been observed 
by some in these formations. 



Fig. 64. 




WW 

Fibrinous coagulurn from a case of plastic bronchitis, (v. Jaksch.) 



Whenever it is desired to examine sputa in this direction it is best 
to pick out particles that look promising upon a dark or light surface, 
and then to shake these out in water in order to unravel them. For 
such purposes Krouig's sputum-plate can be strongly recommended. 

Curschmann's Spirals. Quite distinct from the formations just 
described are the so-called spirals of Curschmann, observed especi- 
ally in cases of true bronchial asthma, but also occurring in chronic 
bronchitis, and even in croupous pneumonia. Upon careful exami- 
nation they will be seen to occur in the form of thick, whitish- 
yellow masses, which exhibit a spirally twisted appearance, and which 



THE SPUTUM. 



219 



are characterized, moreover, by their more solid consistence and light 
color. Microscopically Cnrschmann's spirals are seen to consist of 
a spirally twisted network of extremely delicate fibrils, containing 
epithelial cells and especially leucocytes, which have lately been 
shown to belong almost exclusively to the type of eosinophils. 
Usually, but not invariably, Charcot-Leyden crystals are also seen. 



Fig. 65. 






- 



A Curschmann's spiral from a case of true bronchial asthma. 

The spirally twisted mass is found to be wound around a central, 
very light and clear thread, which usually has a zig-zag course 
(Fig. 65). 

Other formations, probably mere varieties of those just described, 
have also been observed, in which the central thread is absent, or 



Fig. 66. 



Fig. 67. 





Charcot-Leyden crystals. (Scheube. 



Wall of a hydatid cyst, showing 
the laminated structure, not mag- 
nified. (Davaine.) 



in which the spiral arrangement is deficient. The spiral form, 
however, with the central thread, must be considered as the most 
characteristic. Their length and breadth may vary a great deal, but 



220 CLINICAL DIAGNOSIS. 

rarely exceed 1 to 1.5 cm. Their occurrence seems always to indi- 
cate a desquamative catarrh of the bronchi and alveoli, but practically 
nothing is known concerning their formation. If, in a given case, 
the diagnosis rests between true bronchial and what may be termed 
reflex asthma, the presence of these formations points to the exist- 
ence of the former disease. Chemically the spirally wound mass 
seems to consist of a mucinous substance, while the central thread is 
possibly of fibrinous origin. 

Charcot-Leyden crystals (Fig. 66), which are usually absent at 
the beginning of the attack of asthma, at which time only the spirals 
are observed, may be seen to develop from the spirals when these are 
kept for several days. They will be considered later on, when the 
chemistry of the sputum will be studied. 

Echinococcus Membranes. Echinococcus membranes come 
from a perforating cyst of the liver, kidney, or lung. They consti- 
tute rather thick, and at the same time tough, pieces of membrane 
(Fig. 67) ; occasionally entire sacs are seen, of the color of white 
porcelain, in sections of which it is possible to make out a fibrillated 
structure. They are rare in this country. 

Concretions. Still rarer is the expectoration of certain concre- 
tions which have formed in dilated portions of the bronchi or in 
tubercular cavities, or of calcified bronchial glands that have found 
their way into the lungs. Curious examples of the occurrence of 
such concretions have been reported. Andral thus cites a case of 
phthisis in which within eight months as many as 200 stones were 
expectorated, and Portal mentions a case in which 500 were thus 
expelled. 

Foreign Bodies. Foreign bodies which have accidentally en- 
tered the air-passages and may have remained there for a long time 
are also occasionally found in the sputum. Heyfelder mentions a 
case in which a man coughed up a wooden cigar-holder with pus and 
blood after eleven and a half years. 

Microscopic Examination. 

Under this heading it is necessary to consider leucocytes, red blood- 
corpuscles, epithelial cells, elastic fibres, corpora amylacea, parasites, 
and crystals. 

Leucocytes. Leucocytes, usually polynuclear in character, are 
found in every sputum in considerable numbers, imbedded in a homo- 
geneous, more or less tenacious material. At times they appear 






THE SPUTUM. 221 

very granular, containing fat-droplets in their interior, or granules 
of pigment, such as carbon, or lnematoidin. Most interesting is the 
occurrence of large numbers of eosinophilic and even of basophilic 
leucocytes in asthmatic sputa. The number of leucocytes varies a 
great deal, being naturally greatest in cases of perforating abscess, 
empyema, putrid bronchitis, etc. 

Red Blood-corpuscles. The presence of red blood-corpuscles 
in small numbers does not by any means indicate serious pulmonary 
or cardiac disease, as they are found, according to von Jaksch, in 
almost every sputum, and especially in that of individuals who 
smoke much or live in a smoky atmosphere, being, without doubt, 
derived from the catarrhally inflamed bronchial or tracheal mucosa. 
Whenever they occur in large numbers, however, their presence 
becomes importaut. They may thus be observed in acute bronchitis, 
pneumonia, oedema of the lungs, bronchiectasis, abscess, gangrene — 
in fact, in all pulmonary diseases. Their occurrence is most impor- 
tant in phthisis, being, in fact, one of the most constant symptoms 
of the disease. 

The form of the red corpuscles will depend upon the length of 
time that they have remained in the lungs, and all gradations from 
the typical red corpuscle to its shadow, or even fragments, may thus be 
observed. In pneumonia the microscopic examination in* this direc- 
tion may at times be very disappointing, the appearance of the 
sputum suggesting that red corpuscles in large numbers are present, 
while, as a matter of fact, almost all of these may be destroyed, and 
the color be due to altered pigment. It may even be necessary at 
times to depend upon chemical methods to clear up any doubt as to 
the source of the color of the sputum. It should always be remem- 
bered that a red color does not necessarily indicate the presence of 
blood-pigment, but that the latter may assume a golden-yellow or 
even a greenish tinge, having undergone certain chemical chauges. 
The golden-yellow and the grass-green sputa observed in cases of 
pneumonia during convalescence belong to this order. 

Epithelial Cells. Epithelial cells may also be observed in the 
sputum. While a great deal of information would be expected from 
their presence from a diagnostic point of view, as accurately indi- 
cating the parts of the respiratory tract attacked by disease, the 
data obtained are of little value. 

Cylindrical epithelial cells, providing they do not come from the 
nose, indicate in a general way an inflammatory condition of the lower 



_ :i . AZ &IAG50SIS. 

larynx, trachea, or bronchi. They are not of mneh importance, 
however, their form being usually so much altered that it is often 
difficult to recognize thern^ having become polyhedral, cuboidal, or 
o round, so as to be hardly distinguishable from a leucoo 
vely moving cilia can only be found in perfectly fresh sputa, im- 
mediately after being expectorated. If ciliated epithelial cells can be 
definitely recognized in a sputum, it may be inferred that we are 
dealing with a pathological condition of an acute nature, providing, 
of course, they did not come from the nose. 



?r =.-•;• 




n : 



I iiiizn le- : -'-.-■ : _1 :: - ; - ; :: :lr sz~~ ~ - ~~: .r'.r ZZ ::;r-:rlTr * a 7.ri:-rr: 

il"re:.LiT ---"---"- — : — --~--~-- ^ J -- ; - v _"--~ j - ->/ ----- 

- : - 1 -m: :;;_:.:." ~ ■*. / ~Zi:r . : : 1- : :; : - r-ec ':. ;•:•!- 
corpraseJes ; *, squamous epttturiinra. /v. Jjlksch. ) 

Much importance was formerly attached to the so-called alveolar 
epithelial cells (Fig. 68) as an aid in diagnosis. Buhl thus imag- 
ined these, particularly when undergoing fatty or myeline degenera- 
tion, to be absolutely pathognomonic of pulmonary disease, and 
especially of that form of pneumonia which has been termed essen- 
tial idiopathic desquamative pneumonia. Bizzozero, however, as 
well as others, has shown that these cells do not only occur in almost 
every known pulmonary disease, but also in the so-called " normal " 
expectoration which at times is obtained upon making a very forcible 
expiration. 

Bizzozero describes these cells as round, oval, or polygonal bodies, 
varying in size from 20 /* to 50 p. They may contain one, two, or 
three oval nuclei, which are rather small and provided with nucleoli. 
The latter are usually hidden beneath numerous granules. Some of 
these granules are albuminous, but most of them belong to one of 
the following categories: pigmented granules, fatty granules, and 



THE SPUTUM. 



223 



myeline-granules. The myeline-granules were first discovered by 

Virchow in 1854, and termed myeline-granules on account of their 
resemblance to mashed nerve-matter. They are distinguished from 
the other forms by their clear, pale, colorless appearance and the fact 
that at times fine concentric striations can be detected. These forms 
may be round, but more often they are irregular in form. At times 
fatty, myeline, and pigment granules may be seen in one and the 
same cell. Possibly they are derived from the pulmonary alveoli, 
but this is still an open question. 

Liver-cells may at times be observed in the sputa in cases of 
liver-abscess, and are easily recognized by their characteristic form. 

Elastic Tissue. Much more important from a clinical stand- 
point are the elastic fibres and shreds of elastic tissue which may be 
found in sputa. They vary very much in leugth and breadth and are 
provided with a double undulating contour ; they are usually curled 
up at their ends. Very often they exhibit an alveolar arrangement 
(Fig. 69), which at once determines their origin. 



Fig. 69. 




Elastic fibres in the sputum (eye-piece III., objective 8 A, Reichert). (v. Jaksch.) 



Whenever present, elastic tissue is an absolute indication that a 
destructive process is going on in the lungs. It is found in cases of 
abscess of the lung, bronchiectasis, occasionally in pneumonia, and, 
most important of all, in phthisis. In gangrene of the lung, elastic 
tissue is usually not found, probably owing, as suggested by Traube, 
to its destruction by a ferment. 

In every case it is necessary to determine whether the elastic tissue 
may not be owing to the presence of animal food in the sputum, 



224 



CLINICAL DIAGNOSIS. 



and it may, hence, be stated as a safe rule that it can only be 
regarded as absolutely characteristic when showing the alveolar 
arrangement. 

In order to demonstrate the presence of elastic tissue in the spu- 
tum it is necessary to examine large quantities with a moderately 
low power, best after the addition of a strong solution of sodium 
hydrate. The sputum may also be boiled with a 10 per cent, solu- 
tion of the reagent, an equal volume being added ; after dilution with 
four times its own volume of water it is allowed to settle for twenty- 
four hours. The centrifugal machine will here be found of great 
assistance. 

The following method, in use at the Johns Hopkins Hospital, is 
most convenient : "A small amount of the thick purulent portion of 
the sputum is pressed out into a thin layer between two pieces of 
plain window-glass, 15 by 15 cm. and 10 by 10 cm. The particles 
of elastic tissue appear on a black background as grayish-yellow 
spots, and can be examined in situ under a low power. Or the 
upper piece of glass is slid off till the piece of tissue is uncovered, 
when it is picked out and examined on a microscopic slide, first with 
a low and then with a higher power. At first there will be some 
difficulty in distinguishing with the naked eye between elastic fibres 
and particles of bread, or milk-globules, or collections of epithelium 
and debris, but with practice such mistakes are rarely made, and the 
microscope always reveals the difference." (Musser.) 

Fig. 70. 



^ 

c^^ 






Hooks from teenia echinococcus. X 350. 



Animal Parasites. Portions of echinococcus cysts, viz., pieces 
of membrane (Fig. 68) and booklets (Fig. 70 ), are occasionally seen, 
when the parasite has lodged in the lungs or in the neighboring 
organs. The disease however is exceedingly rare in this country. 



THE SPUTUM. 



225 



The adult parasite (Fig. 71), taenia echinococcus, is found in the 
intestinal canal of dogs. It measures fro in 3 to 5 mm. in length. If 
the eggs of the parasite are introduced into the digestive tract of 
man, the embryos may make their way into the lungs, liver, or other 
organs, and there give rise to the formation of cysts, which arc often 
of enormous size. 




Human echinococcus. (From Finlayson, after Davaine.) A, a group ot echinococci, still 
adhering to the germinal membrane by their pedicles X 40. B, an echinococcus with head 
invaginated in the body. X 107. C, the same compressed, showing suckers and hooks of the 
retracted head. D, echinococcus with head protruded. E, crown of hooks, showing the two 
circles. X 350. 

Protozoa have at times been observed in cases of gangrene of 
the lung and in the pus removed post mortem from cavities. Most 
important is the presence of the amoeba coli, as the diagnosis of 
hepatic abscess with perforation into the lung may be made in every 
instance in which the organism is encountered in the sputa (see Feces). 

The existence of pulmonary disease referable to the presence of 
distoma pulmonale, observed almost exclusively in China and Japan, 
may be inferred if the ova of the parasite are found in the sputum. 



Vegetable Parasites. 

Pathogenic organisms. The most important vegetable parasite 
met with in the sputa is the bacillus of tuberculosis. The history of 
the discovery of this organism, and the theories which were held 
before its pathognomonic importance was established, cannot be con- 
sidered here. Suffice it to state that the study of bacteriology has 
given no other discovery of equal importance from a clinical point 

15 



oo,3 CLINICAL DIAGNOSIS. 

of view. How primitive and wholly in; id equ ate the means for- 
mer! v emploved in makiDg the diagn jsis of this, the most formidable 
disease of modern times! Hie presence :: isence .:' elastic tissue 
in the sputa was practically all that physicians formerly had to 
le them, beyond the history :: the patient and the results of a 
physical lamination. The demonstration of elastic tissue, how- 
s has been pointed, out. indicates merely the existence of a 
Lestructive process in the lungs. Under such conditions it was 
of necessity impossible : diagnose tubercular disease in its incipi- 
ency. It is true that cases are occasionally observed in which 
tubercle-bacilli are uevei res nt in the sputa, and are only dis- 

post mortem. Such cases, however, are rare, and do not 
in the least letract from the importance which attaches to careful 
and repeated examinations of the sputa in all doubtful cases. 

From a macroscopic examination it is impossible to decide whethei 
or not : given sputum is of tubercular origin. It may. at times, 

that a certain sputum has a suspicious appearance, but it 
is never possible to speak with certainty from simple inspection, as 
a mucoid sj itum may contain tubercle-bacilli in large numbers, 
while a muco-purulent sputum may be entirely free from them. 
Reliance should, hence, only be placed upon a careful microscopic 
examination. When found their presence is, of course, pathogno- 
nic A negative result, however, does :: exclude the exist- 
ence of tubercular disease. The possibility that they may be alto- 
gethei absent from the i has just been mentioned. In some 

instances they may be present at times and absent at others. In 
all cases in which the existence of phthisis is suspected it is im- 

fcc make use of eve rhich may aid in their detec- 

tion. In this connect ishes to insist strongly upon 

the method of " growing the bacilli, as it were, in the warm-cham- 

:or from twenty-four to forty-eight hours, and then re-examin in 
the sputa in doubtful cases, as Nnttal d _ mstrated beyond a doubt 
that the tub le-1 acillus will multiply in the sputum itself at a 
certain temperature. The value of this iservation is obvious, and 
the author was able lly to demonstrate their presence in 

this manner when it was -ible to detect them in the fresh 

sputum. 

The centrifugal machine in such eases is also useful and yields valu- 
able results, the probabilities of rinding the bacilli when present in 
only small number ig va much increased. 



r 



THE SPUTUM. 227 

If hut few bacilli be present, the following procedure may also be 
employed : About 100 c.c. of sputum are boiled with double the 
amount of water, to which from six to eight drops of a 10 per cent, 
solution of sodium hydrate have been added, until a homogeneous 
solution has been obtained, water being added from time to time 
to allow for evaporation. This is then set aside for twenty-four 
to forty-eight hours, and examined for tubercle-bacilli and elastic 
tissue. 

In the examination of tubercular sputa the fine caseous particles 
described on page 216 should be carefully sought for, as they con- 
tain the largest number of bacilli. In their absence reliance should 
be placed upon the examination of a large number of preparations. 

If, notwithstanding the fact that all due precautions have been taken, 
no bacilli can be demonstrated in the sputum, and providing that the 
clinical history and the physical signs are indefinite or negative, the 
probabilities are that we are dealing with a benign process. From 
an examination of the sputa alone in such cases it is utterly impos- 
sible to reach a definite conclusion. When the amount of sputum, 
moreover, is small and contains but little pus, the absence of tubercle- 
bacilli in doubtful cases is less suggestive of the absence of tubercular 
disease than in cases in which the sputum is more abundant and 
muco-purulent. 

It has been pointed out that the discovery of the etiologic relation 
existing between the bacillus of tuberculosis and tubercular disease, 
notably phthisis, must be regarded as one of the most important for 
the clinician, if not the most important in itself, made by bacteriol- 
ogists. This is certainly true, but the discovery of certain charac- 
teristics of the tubercle-bacillus which are of direct practical utility 
in its recognition and differentiation from other organisms is still 
more important. Reference is had to the behavior of the micro- 
organism toward certain staining-reagents and the difference which 
exists between it and other bacteria, and which renders its recogni- 
tion an easy matter. The bacillus of leprosy might possibly be con- 
founded with the tubercle-bacillus, but it is so rarely met with that 
it need not be considered. 

The tubercle-bacillus is essentially characterized by the difficulty 
with which it takes up basic coloring-matters and the great tenacity 
with which it retains these when once stained upon treatment with 
mineral acids. 

Methods of staining the tubercle-bacillus. Various methods have 



CLINICAL DIAGNOSIS. 

been suggested for the purpose of staining the bacillus, all of which, 
however, are modifications of that suggested by Weigert and Ehr- 
lich. 

1. The Weigert-EhrUeh method: A drop of sputum, or. better, 
one of the cheesy particles described, is carefully spread between 
two cover-glasses ; these are then drawn apart, dried in the air, and 
passed through the name of a Bnnsen burner or of au alcohol lamp 
three times in order to fix the preparations. These are then floated 
for twenty-four hours, face downward, upon a solution of aniline- 
water aud fuchsin prepared in the following manner: 

A small test-tube full of water is shaken for some time with abont 
twentv drops of pure aniline oil 1: 20 . and then filtered through a 
moistened filter after standing for a few minutes. To this solution a 
few drops of a concentrated alcoholic solution of fuchsin or of methyl- 
violet are added until the mixture becomes slightly cloudy — i. >:.. 
until a slightly metallic lustre is noted on the surface. After twenty- 
four hours the preparation is washed with distilled water in order 
to remove an excess of the staining-rluid. The preparation is then 
immersed for several seconds in a dilute solution of nitric or muriatic- 
acid (1 : 6. 1 : 3. or 1:2). and washed again with water or with abso- 
lute alcohol. At this time the preparation should have a faintly red 
or violet color. It is then dried between layers of filter-paper or in 
the air. and mounted in a drop of water. 

If it be desired to make a double stain, which may at times aid 
in the recognition of the organism. Bismarck-brown, vesuvin. or meth- 
ylene-blue in watery solutions may be used for this purpose. Into 
this solution the specimen is placed after treatment with nitric acid 
and washing in water. 

2. Gabeffs method : The dried preparation is placed for two min- 
utes in a solution composed of 1 part of fuchsin (S), 100 parts of a 5 
per cent, solution of carbolic acid, and 10 parts of absolute alcohol, 
and then immediately transferred for one minute to a solution of 2 
parts of methylene-blue in 100 parts of a 25 per cent, solution of 
sulphuric acid. It is then washed with water and mounted. 

3. Zi - j method: A mixture of 90 parts of a 5 per cent. 
solution of carbolic acid and 10 parts of a c^nz-entrated alcoholic solu- 
tion of fuchsin is used. The procedure to be followed is the same as 
that described under the TVeigert-Ehrlieh method. 

When method 1 or 3 is used, however, it is unnecessary to stain 
the preparation for twenty-four hours, it being sufficient to place a 






PLATE VII. 



V i 






// 



Vi \\ 



> -:$rf- 



,,',- -\,> 



Tuberculous Sputum stained by Gabbett's Method. The tubercle bacilli 
are seen as red rods, all else is stained blue. (Abbott.) 

FIG. 2. 




The Diplococcus Pneumoniae. 
FIG. 3. 






€1 



W 



$0 






Aft* 



> 



Heart-Disease Cells, showing Alveolar Epithelial Cells, loaded 
down with Granules of Hsematiu. 



THE SPUTUM. 229 

few drops of the staining-fluid upon the cover-glass and to boil this 
for a few seconds over the Vivo flame, when the specimen is further 

treated as described. In this manner excellent results may be obtained 
in a few minutes. 

Stained according to one of these methods, the bacilli appear as rods 
measuring about 3 y. to 4 a in length, by 0.3// to 0.5 fjt in breadth 
(Plate VIL, Fig. 1). Usually they are not swollen at their ex- 
tremities, but simply rounded off. They form homogeneous rods or 
may present small round or ovoid granules placed end to end, which 
do not stain. Their form may also vary from a straight rod to a 
curved body, or the bacillus may even appear to be doubled up upon 
itself in the form of the letter S. The small hyaline bodies in the 
bacilli have been regarded as spores. 

The number of bacilli which may be found in a sputum varies 
greatly, and while in general it may be said that the number of 
bacilli is proportionate to the intensity of the disease, and may 
thus be considered as of some prognostic value, too much reliance 
should not be placed upon this statement, as in acute miliary tuber- 
culosis, and in cases that have gone on to the formation of cavities, 
the walls of which have become dry and cicatrized, the number 
found may be very small, or the bacilli may be altogether absent. 
In an incipient case, on the other hand, in a little mucoid sputum the 
number may be very large. 

Of the variations in number and form of the tubercle-bacilli dur- 
ing the treatment with Koch's tuberculin it is unnecessary to speak 
here, as the prognostic significance attaching to such variations is as 
yet but imperfectly understood. 

In doubtful cases the sputum may be examined for the diplococcus 
pneumonice, and it may be accepted at the present time that its pres- 
ence in a given case, providing that the clinical history and the phy- 
sical signs point to a pneumonia, renders the diagnosis of the disease 
a very probable one. 

Method: Cover-glass specimens, prepared as indicated above, are 
placed for one or two minutes in a 1 per cent, solution of acetic acid ; 
they are then removed, the excess of acetic acid drawn off by 
means of a pipette, when they are allowed to dry in the air and sub- 
sequently placed for several seconds in saturated aniline-water and 
gentian-violet solution, washed in water and examined. Rod-shaped 
diplococci (Plate VII., Fig. 2) surrounded by a capsule, which latter 



230 CLINICAL DIAGNOSIS. 

sidered as the characteristic feature ol this microbe, will be seen 
in cases of acute croupous pneumonia. 

The bacillus of influenza has already been considered in Chapter I. 

i P . -- 

In whooping-t rotozoa have been observed byDeiehler; his 

rations, however, have not as vet been confirmed, and other 
observers attribute the disease to the presence of a bacillus described 
by Affanasiew. 

Actinomycosis of the lungs may possibly be diagnosed from the 
presence of the characteristic granules and thread-like formations in 
the sputum. In America the disease is very rare. 




The organism in question Fig. 72 probably belongs to the species 
eladothrix, occupying a unique position among the pathogenic bac- 
teria. Infection in man and animals cattle and pigs possibly 
occurs through ears of barley or rye. a supposition with which the 
observation that the disease frequently begins in the autumnal months 
accords. 

In the pus derived from ulcerating actinomycotic tumors, in the 
sputum in cases of pulmonary actinomycosis, as also in the feces 
when the disease has attacked the intestines, small yellow granules 
will be : sei ed 3 measuring from O.o to 2 mm. in diameter. If such 
a granule be examined microscopic-ally, slight pressure being applied 
to the cov it will be setn to consist of numerous threads. 

which radiate out from a centre in a fan-like manner, and present 
club-shaped extremiti 

The organism may be demonstrated in the following manner: Dried 



THE SPUTUM. 

cover-glass preparations are stained for five to ten minutes with a 
saturated aniline-water and gentian-violet mixture (see p. 228), when 
they are rinsed in normal salt-solution, dried between filter-paper, 
and transferred for two or three minutes to a solution of iodo-potassic 
iodide (1:2: 100). They are then again dried between layers of filter- 
paper, decolorized in xylol-aniiine oil (1 : 2), washed in xylol, and 
mounted in balsam. The mycelium assumes a dark-blue color. 

Non-pathogenic organisms. Of the non-pathogenic micro-organ- 
isms which may be observed in sputa but very little is known. 

Galium albicans may be observed in children, and is usually derived 
from the mouth. 

Of other fungi which are occasionally observed in the sputum, 
there may be mentioned the aspergillus fumigatus and mucor corym- 
bifer. Saccharomyces has been seen in the pus derived from pul- 
monary abscesses. Sarcina puhnonalis has been found at times, and 
especially in the so-called mycotic bronchial props occurring in 
putrid bronchitis. They are usually smaller than the sarcinse ven- 
triculi, but larger than the sarcina? observed in the urine ; they pre- 
sent the characteristic form of the latter. Various other bacilli and 
micrococci, in addition to those mentioned, are also found in sputa 
in large numbers, but have not as yet been closely studied, excepting 
the pus-organisms, which may be almost always demonstrated. 

Crystals. Of crystals which may occur in sputa it will be necessary 
briefly to consider the crystals of Charcot-Leyden, hsematoidin, cho- 
lesterin, margarin, tyrosin, oxalate of calcium, and triple phosphates. 

Charcot-Leyden crystals (Fig. 66) were discovered in the sputa of 
patients suffering from asthma, and were supposed to stand in a causa- 
tive relation to the disease. While it is true that the crystals are 
seen especially in this disease, they are also exceptionally met with 
in acute bronchitis, chronic bronchitis, phthisis pulmonalis, etc. 

Chemically, they appear to be phosphate of spermin, which has the 
composition C 2 H 5 N, and has been shown to be identical with ethylen- 
imine. The phosphate crystallizes in the form of colorless, elongated 
octahedra, which vary very much in size, specimens being at times 
met with measuring from 40 jjl to 60 (i in length. The substance 
is soluble with difficulty in cold water; insoluble in alcohol, ether, 
chloroform, and dilute saline solution ; slowly soluble in acids and 
alkalies and even in ammonia. The formula given and the fact 
that the same crystals are found in decomposing viscera, at times 
forming a complete covering of old anatomical preparations, render 



232 CLINICAL DIAGNOSIS. 

the supposition very probable that the substance in question is closely 
related to the ptomaines ; the crystals may, indeed, be regarded as 
indicating a retrogressive metamorphosis of the cellular elements of a 
part. They are found not only in the sputa of the diseases mentioned, 
but also in leukemic blood, in the mucus which has accumulated 
in a dilated biliary duct, and in normal and leukemic bone-marrow. 
As has been stated, the crystals are also quite constantly met with in 
the feces in ankylostomiasis, anguilluliasis, and other helminthiases 
(see p. 181). Bizzozero found them in his own sputum at times 
when suffering from a simple acute bronchitis. 

Hcematoidin-cry state may be observed in the sputa following extrav- 
asation of blood into the lung. They occur in the form of ruby-red 
columns or needles (Plate I., Fig. 2) ; amorphous granules are also 
at times seen enclosed in the bodies of leucocytes, in which latter case 
they are probably always indicative of a previous hemorrhage, while 
the presence of needles is generally observed in cases in which an 
abscess or empyema has perforated into the lungs. Chemically, 
haematoidin is derived from blood-pigment, and appears to be closely 
related to bilirubin. 

Cholesterin-cry state are at times seen in the sputa in cases of phthisis, 
pulmonary abscess, and in general whenever pus has entered the 
lung from a neighboring organ and has become stagnated. They 
are very readily recognized by their characteristic form and chemical 
properties (see Feces, p. 172). 

Fatty-acid crystals are frequently observed in cases of putrid bron- 
chitis and gangrene of the lung, and also in cases of bronchiectasis 
and phthisis. They occur in the form of single needles, or groups of 
needles, which are long and pointed. They are easily soluble in ether 
and hot alcohol; insoluble in water and acids. Chemically, they are 
probably composed of the higher fatty acids, such as palmitic and 
stearic acids. 

Tyrosin-cry state have been observed in cases of putrid bronchitis, 
perforating empyema, etc. Leucin is likewise probably always 
present, occurring in the form of highly refractive globules. For 
the recognition of these bodies, particularly tyrosin, a chemical 
examination should always be made, as crystals of the soaps of 
fatty acids have frequently been mistaken for those of tyrosin (see 
Urine). 

Oxalate of calcium crystals are rarely seen. Fiirbringer observed 
them in large numbers in a case of diabetes, and Unger found them 






THE SPUTUM. 233 

in a rase of asthma. They are readily recognized by their envelope- 
form, but they occur also in amorphous masses. They arc soluble in 
mineral acids; insoluble in water, alkalies, organic acids, alcohol, 
and ether. 

Triple phosphate crystals are also, though very rarely, Been, as in 
cases of perforating abscess, etc. They are recognized by their coffin- 
lid shape and the readiness with which they dissolve in acetic acid. 

Chemistry of the Sputum. 

In addition to the substances described, sputum contains certain 
albumins, volatile fatty acids, glycogen, ferments, and various inor- 
ganic salts. 

Among the albumins which have been observed in sputa may 
be mentioned serum-albumin, but especially mucin, which is often 
present in large amounts. In pneumonic and purulent sputa peptone 
also has been found. 

In order to demonstrate the presence of serum-albumin the sputa 
are treated with dilute acetic acid, when the filtrate may be tested 
with potassium ferrocyanide, as described in the chapter on Urine. 
Serum-albumin is, of course, found in notable quantities in cases of 
oedema of the lungs. 

The volatile fatty acids contained in sputa may be obtained by 
diluting the latter with water, acidifying with phosphoric acid, and 
distilling, when the distillate is further examined as described in 
the chapter on Feces. Acetic acid, butyric acid, propionic acid, and 
capronic acid have been found. 

The fats or fixed fatty acids are extracted from the residue with 
ether, and shaken with a solution of sodium carbonate in order to 
transform them into their sodium salts, when the ether is decanted 
and evaporated, leaving the fats behind. 

Glycogen has been repeatedly demonstrated in sputa and may be 
detected by JBrlicke's method. (See p. 42.) 

The sputa of gangrene of the lungs and putrid bronchitis have 
been shown to contain a ferment resembling trypsin. In order to 
test for this ferment the sputa are extracted with glycerine, and the 
examination continued as described in the chapter on the Exam- 
ination of Cystic Contents. 

The following are the inoganic salts which may be demonstrated 
in the sputum: The chlorides of sodium and magnesium, phosphates 



234 CLINICAL DIAGNOSIS. 

of the alkalies and the alkaline earths, viz., calcium and magnesium, 
the sulphates of calcium and sodium, carbonates, phosphate of iron, 
and silicates. 

The Sputa in Various Diseases. 

Acute Bronchitis. In the beginning of the disease the expectora- 
tion is small in amount, transparent, and contains very few cellular 
elements, constituting the so-called sputum crudum of the ancients. 
Microscopically there is evidence of the existence of a desquamative 
process, extending toward the pulmonary alveoli to a greater or less 
extent, implicating especially the bronchi and trachea. Epithelial 
cells of various forms are found, being probably all derived from 
cells which were originally ciliated. Ciliated cells as such may 
occasionally be observed in perfectly fresh specimens, but are 
usually absent. Leucocytes in small numbers and alveolar cells 
are also seen. The presence of a few red blood-corpuscles is a 
common occurrence, being probably due to rupture of a capillary 
bloodvessel. Later on the sputa become more abundant, opaque, 
and assume a yellow color tending to green, owing to an increase in 
the number of leucocytes, while the other cellular elements diminish 
in number. 

Chronic Bronchitis. The amount and consistence of the spu- 
tum in this condition vary greatly ; it is most abundant in cases 
of so-called bronchorrhcea, in which whole mouthfuls may be ex- 
pectorated at a time. The color is usually a yellowish-green, owing 
to the presence of numerous pus-corpuscles in various stages of de- 
generation. Microscopically enormous numbers of micro-organisms 
are found, especially in cases in which the sputa have remained for 
some length of time in the bronchi. In addition some red cor- 
puscles and epithelial cells are found ; the latter, however, are not 
so abundant as in the first stage of an acute bronchitis. A few 
alveolar epithelial cells will also usually be discovered, presenting the 
appearance of fatty and myeline degeneration, as in the case of 
acute bronchitis. 

Putrid Bronchitis and Pulmonary Gangrene. The sputa of 
putrid bronchitis and pulmonary gangrene resemble each other so 
closely that it is only possible to distinguish between the two by the 
presence of debris of pulmonary parenchyma in the latter disease. 
In pulmonary gangrene an exquisite sedimentation is also quite com- 
monly observed when the sputum is placed in a conical glass, the 



f 



THE SPUTUM. 235 

bottom layer being of a greenish-yellow or brownish color, contain- 
ing a large amount of pus and small greenish or brownish masses, 
varying in size from that of a millet-seed to that of a bean. Frag- 
ments oi' lung-tissue are also quite commonly observed. Microscop- 
ically more or less degenerated leucocytes, crystals of ammonio- 
magnesium phosphate, and perhaps also oi' ty rosin and leucin, as 
well as lneinatoidin, are found. The greenish or brownish masses 
referred to contain amorphous masses of pigment, probably derived 
from haemoglobin, at times elastic tissue, fatty-acid crystals, fat-drop- 
lets, and innumerable micro-organisms, among which the leptothrix 
pulmonalis is quite conspicuous, and may be recognized by the violet 
or bluish color which it asumes when treated with Lugol's solution. 
Most important in the differential diagnosis between this affection 
and putrid bronchitis is the occurrence of elastic fibres arranged in 
an alveolar manner. The middle layer is whitish, transparent, and 
contains flakes of mucus in suspension. The superficial layer is 
frothy and of a dirty greenish-yellow color, the entire mass emitting 
an odor never to be forgotten. 

Fibrinous Bronchitis presents all the characteristics of an ordi- 
nary chronic bronchitis, the sputa, however, containing in addition 
well-defined fibrinous casts, which have been described (see p. 217). 

Bronchial Asthma. In this affection, and especially at the com- 
mencement of an attack, the amount of expectoration is very slight, 
frothy, grayish, or at times rose-eolored, owing to an admixture of 
blood. Most characteristic are plug-like masses of a greenish-yellow 
or grayish color, contain ing; spirals of Curschmann, Charcot-Leyden 
crystals, and a large number of eosinophilic and some bosophilic 
leucocytes. 

Pulmonary Abscess. The sputum as long as it is fresh does 
not emit a fetid odor, thus differing from that observed in cases of 
gangrene of the lung. It consists almost entirely of pus ; elastic 
fibres are present in abundance, as also brownish or yellow pigment- 
haernatoidin. Fragments of lung-tissue have at times been observed, 
enclosed in a mass of pus, together with fatty-acid and cholesterin- 
crystals. 

Abscess of the Liver with Perforation into the Lung. The 
sputa are of a reddish-yellow or reddish-brown color, viscid and 
muco-purulent, being frequently discharged in large amounts. Micro- 
scopically, pus-corpuscles, red blood-corpuscles, pigmented alveolar 
cells, often undergoing fatty degeneration, as well as elastic tissue aud 



236 CLINICAL DIAGNOSIS. 

granular detritus, are found. The presence of actively moving amoeba? 
is, of course, most important from a diagnostic point of view, and 
is at the same time absolutely pathognomonic. Liver-cells, pieces 
of echinococcus-membranes, and hooklets may be observed in other 
cases. 

Pneumonia. A simple catarrhal sputum is observed during the 
first and third stages which does not offer any special character- 
istics. During the second stage, however — i.e., that of hepatization — 
the sputum is usually quite characteristic. Its color is then reddish- 
brown — the classical rust-colored expectoration. The sputum at 
the same time is generally so tenacious that the spit- cup can actu- 
ally be inverted without losing a drop of its contents. Microscop- 
ically the following elements may be found : red corpuscles (to the 
presence of these the reddish color is principally due) ; at times, 
however, only a small number is observed, when the color is refer- 
able to haemoglobin which has been dissolved out from the corpus- 
cles, and in such cases but few, if any, corpuscles are found. Leuco- 
cytes are always present in considerable numbers. Fibrinous casts 
of the finer bronchioles may also be seen, and may, in fact, be visi- 
ble to the naked eye. Alveolar epithelial cells, often loaded with 
granules of pigment, fat, and myeline, as well as others derived from 
the larger bronchi and trachea, are also seen. Should abscess of the 
lung or gangrene complicate the case, the elements described above 
under these headings will be found in addition, the presence of elastic 
tissue being, of course, the most important. 

Note may be taken at the same time of the occurrence of pneumo- 
cocci, bearing in mind, however, that their presence is not absolutely 
pathognomonic. In doubtful cases, as indicated, their presence may 
be regarded as pointing to croupous pneumonia, providing that the 
clinical history and the physical signs are in accord. 

Phthisis Pulmonalis. The appearance of the sputum in phthi- 
sis offers nothing that is characteristic, depending wholly upon the 
stage of the disease, its extent, the existence of complications, etc. 
In a general way it may be said that the sputa in incipient cases are 
usually small in amount, of a grayish-yellow color, and tenacious, the 
amount increasing gradually as the disease progresses, the largest 
quantities at this stage being expectorated in the morning upon 
rising. When well advanced the nummular sputa are seen. The 
macroscopic examination of the sputa of tubercular patients orfers 
no characteristic features, the elements found being practically the 



THE SPUTUM. 237 

same as those observed in cases of simple chronic bronchitis, with 
one exception — /. c, the occasional admixture with blood, which 

is usually visible to the naked eye, but may vary greatly in amount. 
Ou the one hand, small specks or streaks of blood may be thus 
observed, while, on the other, the sputa may consist almost 
entirely of blood. The color of the sputum is, of course, largely 
influenced by the amount of blood present and the length of time 
that the latter has remained in the lungs, varying from a bright 
red to a dirty brown. In cases in which a considerable hemorrhage 
has taken place it is, of course, necessary to exclude every other 
source before attributing the hemorrhage to a pulmonary origin, and 
in cases of rupture of an aueurism, or long-continued hyperaemic 
conditions of the lungs so frequently observed in cases of heart-dis- 
ease, in hemorrhage of gastric origin, and in hemorrhage from the 
mouth or pharynx it may at times be difficult to determine the 
source of the blood. 

The diagnosis of phthisis is thus altogether dependent upon a 
microscopic examination, and, above all, upon the demonstration of 
the presence of tubercle-bacilli and elastic tissue, which have both 
been considered in detail. In addition, leucocytes, alveolar epithelial 
cells, hrematoidin-crystals, and granules are met with, which latter 
may be present in large numbers, if a hemorrhage have occurred 
some time before. If the process has gone on to the formation of 
cavities, various constituents are also observed pointing to putre- 
factive processes taking place in the lung. 

CEdema of the Lungs. The sputa here are abundant, thin, 
liquid, and frothy, the color of the foam varying from white to a 
dirty reddish-brown. Chemically, such sputa consist almost entirely 
of transuded serum, and are hence particularly rich in serum-albumin. 
Microscopically, only a small number of leucocytes and a variable 
number of red blood-corpuscles are found, the number of the latter, 
however, being scarcely large enough to account for the red color ; 
von Jaksch ascribes it to the presence of rnethsemoglobin. 

Heart-disease. The sputa observed in chronic bronchitis the 
result of chronic heart-disease are characterized by the presence of 
so-called ^heart-disease cells" — i.e., alveolar epithelial cells con- 
taining numerous hsematoidin-granules (Plate VII., Fig. 3). If, 
in consequence of the existence of chronic heart-disease, hemorrhagic 
infarcts have occurred in the lungs, the patient may at times expec- 
torate numerous masses presenting a markedly red color, while 



238 CLINICAL DIAGNOSIS. 

later on — i. e., after several days — these masses assume a brownish- 
red appearance, the sputum then presenting the characteristics noted 
some time after a hemorrhage. 

The Pneumoconioses. Among the pneumoconioses, anthracosis, 
siclerosis, chalicosis, and stycosis may be briefly considered. These 
conditions are interesting not only from a physiologic but also from 
a pathologic standpoint. 

Anthracosis. To some extent particles of carbon may be found 
in the sputum of almost every individual, and especially in tobacco- 
smokers. The sputum in such cases is of a pearl-gray color, and is 
expectorated in larger or smaller masses, especially in the morning 
upon rising. Larger amounts are, of course, noted in miners and 
those who are brought into close contact with coal-dust. Micro- 
scopically particles of carbon and epithelial cells, especially of the 
alveolar type, as well as leucocytes, loaded with the pigment, are 
seen. 

Siderosis. In siderosis the sputum presents a brownish-black 
color and contains cells enclosing particles of the oxide of iron. 
These may be readily recognized by treating the preparation with a 
drop of ammonium sulphide or potassium ferrocyanide solution in 
the presence of muriatic acid, as a black color on the one hand and a 
blue color on the other is obtained in the presence of iron. 

Chalicosis. In chalicosis silicates are found in the sputa. 

Stycosis. This condition was described for the first time by 
A. Robin in a man, aged seventy, who from his seventeenth year 
suffered from cough and frequent attacks of diarrhoea, and whose con- 
dition had been diagnosed as phthisis pulmonalis et intestinarum at 
various times, no examination having been made for tubercle-bacilli. 
The patient died from acute pericarditis complicating an attack of 
acute mono-articular rheumatism. Post mortem the lungs were found 
to be perfectly normal; the bronchial and anterior mediastinal glands, 
as well as the mesenteric glands, however, were completely solidified 
and composed almost wholly of calcium sulphate. The man, it was 
then found, had been working in plaster-of-Paris all his life, and 
the symptoms observed, viz., cough, expectoration, and diarrhoea, 
Robin is inclined to attribute to pressure of the solidified glands 
upon the lungs and intestines. 



CHAPTER VII. 

THE URINE. 

GENERAL CONSIDERATIONS. 

This is not the place to enter into a discussion of the various 
hypotheses which have been advanced from time to time in order to 
explain the exact manner in which waste-material is removed from 
the body through the kidneys. It will be sufficient to state here, 
that while the water and mineral constituents of the urine undoubt- 
edly pass into the uriniferous tubules by a process of transudation, 
a selective glandular activity of the cells lining the convoluted 
tubules and the loop of Henle at least appears to be necessary for 
the elimination of the most important organic constituents. 

As the physical characteristics of the urine, as well as its chemical 
composition, are influenced not only by the age and sex of the indi- 
vidual, but also by the character of the food ingested, the process of 
digestion, exercise, climate, temperature, race, etc., it is apparent that 
a quantitative analysis of any one urine, or even average figures, can 
give only an approximate idea of its composition. The reader is 
referred for information to the special paragraphs concerning the vari- 
ations in the individual constituents observed in health. It is impor- 
tant, however, to note that, notwithstanding the fairly wide variations 
here observed, the composition of the blood, as already pointed out in 
a previous chapter, remains quite constant, showing the perfect man- 
ner in which the nervous system through the kidneys guards against 
an undue accumulation of what may be termed normal waste-pro- 
ducts in the blood, and in virtue of which abnormal substances are 
also immediately eliminated. Moreover, as will be pointed out later 
on, a perfect mechanism appears to exist which prevents an undue 
accumulation of material in the blood that can hardly be regarded as 
waste. The presence of an amount of sugar in the blood exceeding 
6 p. m., for example, appears to be invariably followed by glyco- 
suria, and the introduction of excessive quantities of sodium chloride 
similarly and almost immediately leads to an elimination of the 
excess. 



240 CLINICAL DIAGNOSIS. 

GENERAL CHARACTERISTICS OP THE URINE. 
General Appearance. 

Normal urine, just voided at au ordinary temperature, is either 
perfectly clear or but faintly cloudy, owing to the fact that the acid 
and normal salts present are all soluble in water. It may be stated, 
as a general rule, that whenever a urine freshly passed manifests a 
distinct cloudiness some abnormality must exist. 

When allowed to stand for a time a light cloud is seen to develop, 
which gradually settles to the bottom, constituting the so-called 
nubecula of the ancients. Examined under the microscope this is 
found to contain a few round, granular cells, somewhat larger than 
normal leucocytes, the so-called mucous corpuscles, and a few pave- 
ment-epithelium cells, derived from the bladder or genital organs. 
Chemically the nubecula probably consist of traces of mucus. 

When kept for twenty-four hours at an ordinary temperature 
some crystals of uric acid are frequently observed in addition to the 
above elements, usually presenting the so-called whetstone-form. If, 
however, the temperature at which the urine is kept approaches the 
freezing-point, the entire volume of urine becomes cloudy, owing to 
a precipitation of acid urates. As these are very much less soluble 
in cold than in warm water, they gradually settle to the bottom of 
the vessel, forming what is known as a sediment while the super- 
natant fluid again becomes clear. 

If kept for a still longer time exposed to the air at the tempera- 
ture of the room, the entire volume of urine again becomes cloudy, 
owing to a diminution of its normal acidity, the result being a precip- 
itation of ammonio-maguesium phosphate, calcium phosphate, and 
still later, when the urine has become alkaline, of ammonium urate. 

Gradually a heavy sediment, containing these salts in addition to 
the constituents of the primitive nubecula, forms at the bottom of 
the vessel, the supernatant fluid, however, remaining cloudy. On 
microscopic examination it will be seen that this cloudiness is due to 
the presence of enormous numbers of bacteria. 

The changes which take place in a normal urine, when allowed to 
stand at an ordinary temperature, may thus be tabulated as follows : 
I. Urine clear, no sediment — reaction acid. 
II. Urine slightly cloudy owing to the development of the 
nubecula — reaction acid. 



x T . / Mucous corpuscles 

Nubecula i ^ . . ,. 

I ravement-epithelia 



Pavement-epithelial cells. 



THE URINE, 241 

III. Urine clear, the nubecula lias settled — reaction acid. 
[ Mucous corpuscles, 

Sediment ; Epithelial cells, 

I Uric-acid crystals, 
1^ A few bacteria. 

IV. Urine cloudy, owing to the precipitation of phosphates — 
reaction faintly acid. 

V. Urine cloudy, owing to the presence of bacteria — reaction 

alkaline. 

r Bacteria, 

Mucous corpuscles, 

,. Epithelial cells, 

Sediment < \ \ 

Inple phosphates, 

Tri-calcium phosphate, 

^ Ammonium urate. 

Color. 

The color of normal urine may vary from a very light yellow to 
a brownish-red, the particular shade depending essentially upon the 
specific gravity, becoming lighter with a diminishing, darker with an 
increasing density. Pathologically the same rule holds good, except- 
ing the urines of diabetic patients, in which a very high specific 
gravity is generally associated with a very light color. The reaction 
of the urine also exerts a marked influence upon its color, an acid 
urine being more highly colored than an alkaline urine, which can 
be readily demonstrated by allowing a specimen of acid urine to 
become alkaline, and by treating an alkaliue urine with dilute hydro- 
chloric or acetic acid. At the same time it may be said that every 
urine darkens slightly on standing, the reaction remaining acid. 

The various shades observed in normal urines may be grouped 
under the following headings : 

1. Pale urines vary from a faint yellow to a straw-color. 

2. Normally colored urines are of a golden or of an amber- 
yellow. 

3. Highly colored urines present a reddish-yellow to a red color. 

4. Dark urines vary between brownish-red and reddish-brown. 
As these shades may occur both in normal and pathologic urines, 

definite conclusions cannot, as a rule, be drawn from mere inspec- 
tion. A very pale urine simply indicates the presence of an abnor- 

16 



242 CLINICAL DIAGNOSIS. 

mally large quantity of water, which may be physiologic, but may 
also be associated with such diseases as chronic interstitial nephritis, 
diabetes mellitus, diabetes insipidus, hysteria, and the various anae- 
mias, and may also occur during convalescence from acute febrile 
diseases, while a highly colored urine, also occurring in health, may 
indicate the existence of some febrile disease. It may be stated, as 
a general rule, that a pale urine always excludes the existence of 
a febrile disease of any severity, and that the continued secretion 
of a very pale urine is usually associated with a certain degree of 
anaemia. 

The normal color of the urine is probably owing to the presence 
of several pigments, which are most likely closely related to each 
other and to haematin. In addition to these colors others may be 
observed at times, which are either pathologic or accidental ; i.e., due 
to the presence of certain drugs. The former are, on the whole, of 
greater importance to the physician than those mentioned above, 
as more definite conclusions can be drawn from their presence. 

Most important among such pathologic pigments are those due: 

1. To the presence of blood coloring-matter. The urine in such 
cases presents a tinge which may vary from a bright carmine to a jet- 
black, the exact shade depending upon the quantity of blood coloring- 
matter present, upon any change that the blood may have undergone, 
either before or after being passed, and also upon the presence of the 
pigment in solution or adherent to red corpuscles. 

2. Those due to the presence of biliary coloring-matter. The 
color of the urine varies from a greenish-yellow to a greenish -brown. 

3. A milky-colored urine is observed in cases of chyluria. 
Among the accidental abnormalities in color, on the other hand, 

are those due to the presence of substances like carbolic acid and its 
congeners, santonin, etc. 

As the recognition of the causes of such alterations, normal, 
pathologic, and accidental, largely depends upon a more detailed 
study of the individual pigments, this subject will be dealt with 
more fully further on (see Pigments). 



Odor. 

The odor of the urine is usually of little significance. Normally 
it resembles that of bouillon, and in some cases oysters ; it is prob- 
ably due to the presence of several volatile acids. The odor of 



THE URINE. 243 

urines undergoing decomposition is characteristic and has been termed 
"the urinous odor of urine," an ill-chosen term, this odor being 
always indicative of an abnormal condition. 

The ingestion of asparagus, oil of turpentine, etc., produces a 
characteristic odor which is of no significance. 

Consistence. 

Urine, while normally fluid and but slightly viscid, may in patho- 
logic conditions acquire a marked degree of viscidity, which becomes 
especially apparent upon attempting its filtration ; the liquid passes 
through the paper with more and more difficulty, finally clogging 
its pores altogether. 

Quantity. 

The normal quantity of the urine is subject to great variations, 
the amount eliminated in the twenty-four hours being influenced by 
the amount of fluid ingested, the nature and quantity of the food, 
the process of digestion, the blood-pressure, the surrounding tem- 
perature, sleep, exercise, body-weight, sex, age, etc. 

It is easy to understand, then, why the figures given by different 
observers in different countries should vary considerably. Salkowsky, 
in Germany, thus gives 1500 to 1700 c.c. as the normal amount; 
von Jaksch, in Austria, 1500 to 2000 c.c. ; Landois and Sterling, in 
England, 1000 to 1500 c.c; Gautier, in France, 1250 to 1300 c.c. 
In the United States the author has found an average secretion of 
from 1000 to 1200 c.c. in the adult male and 900 to 1000 c.c. in the 
adult female. It is thus seen that the secretion of urine is greatest 
in Germany and Austria, where the body-weight and ingestion 
of liquids are greater than in England, France, and the United 
States. 

Children pass less, but relatively more urine, considering their 
body-weight, than adults. 

The female passes somewhat less than the male. 

During the summer months, when a larger proportion of water is 
removed from the body through the skin and lungs than in cold 
weather, less urine is voided. The same occurs during repose, more 
urine being passed during active exercise, and hence less during the 
night than during the day. 

The amount of urine secreted in the different hours of the day 



244 CLLSICAL DIAGSOSIS. 

;hing its maximum a few hours after meals. It 
deere:" - rd night, and reaches its lowest point in the first hours 

of the night, after which it begins to rise rapidly until 2 or 3 o ! : 
in the morning. 

The ingestion of large amounts of liquid, of course, increases the 
daiiv amount considerably, and 3000 c.c. may be passed by a man 
■ health, while i: may ilecrease to S Ml i :>v 900 c.c. when but 
little liquid is taken. 

After the ingestion of much solid food the secretion of urine is 
temporarily diminished. 

"Water containing no salts appears to possess diuretic properties, as 
do also beer. wine. rfee. tea. etc. 

The most important medical diuretics are digitalis, squill, broom, 
spirits of nitrous ether. Juniper, urea, etc. 

Pathologically the amount of urine varies within very wide limits. 
It may be exceedingly difficult, however, to determine in a given 
;-ase whether or not the secretion be within physiologic limits. As a 
general rule, whenever less than 500 c.c. or more than 3000 c.c. 
are passed seme abnormal condition is present, providing ail other 
[•auses which might lead to the secretion of such an amount can be 
eliminated. 

Clinically we speak of polyuria and oliguria. 

Polyuria. Polyuria has been observed in many different diseases, 
and under such varied conditions that a classification is at present 
only warrantable upon a hypothetic basis, especially as the causes 
ned in its production are mostly unknown. 

As this con >n is almost invariably associated with diabetes 
mellitos, its existence in any case should always excite suspicion 
and lead to a more detailed examination. The quantity of fluid 
eliminated in diabetes is usually dependent upon the amount in- 
gested. The excretion of a proportionately large amount of fluid. 
however, does not necessarily follow the ingestion directly, and a 
retention of a large amount may occur, it having been shown 
that the diabetic patient excretes liquids with greater difficulty 
than the healthy subject. At the same time it should be borne 
in mind that the polyuria in diabetes is not necessarilv continuous, 
and that periods during which a normal or even a subnormal amount 
of urine is observed may alternate with true polyuria. From 2 to 26 
or even 50 liters may ssed within twenty-four hours. Inter- 

current diseases of a febrile character mav modify the amount very 



the mux/:. 945 

materially and cause the elimination of a normal or subnormal 
amount of urine. 

The cause of the polyuria occurring in diabetes mellitns is at 
present unknown. The ingestion of large amounts of liquids, of 
course, leads to a correspondingly large elimination, and the exist- 
ing polydipsia could, hence, be made responsible for the polyuria, 
and the latter be the result of an increased stimulation of the thirst- 
centre, possibly owing to the presence of some abnormal constituent 
of the blood. The polydipsia, however, may also be the result of a 
primary polyuria. 

The polyuria associated with the resorption of large pericardial, 
pleural, ascitic, and subcutaneous effusions is more readily under- 
stood, although the primum mobile may be unknown, depending in 
such cases entirely upon the presence of excessive quantities of fluid 
in the bloodvessels. 

A form of polyuria, which has been termed " epicritic polyuria/' 
is quite frequently observed during the convalescence from acute 
febrile diseases, and is of some prognostic importance. Its occur- 
rence in a given case is regarded by many as a good omen, especially 
in typhoid fever ; still it must not be forgotten that a polyuria 
may occur after the disappearance of the fever, and be followed by 
a considerable degree of oliguria, and in some cases may precede death. 
A polyuria of this kind probably always indicates the elimination 
of waste-products which had accumulated in the blood during the 
course of the disease, and may, at the same time, to some extent, be 
due to the presence of retained water. 

Second in constancy is the polyuria associated with granular atro- 
phy of the kidneys, constituting one of the most important symptoms 
of the disease. Cases have been reported in which as much as 10,000 
c.c. of urine were secreted in the twenty-four hours, although 2000 to 
4000 c.c. probably represent the usual amount in such cases. Poly- 
dipsia exists at the same time, and the explanation of the polyuria thus 
again becomes a very difficult matter. The explanation usually given 
is based upon the following considerations: 

In granular atrophy of the kidneys large tracts of renal paren- 
chyma are undergoing destruction, the result being a diminution in 
the area of glandular material, which in itself could lead to a dimin- 
ished secretion of urine. The coexisting cardiac hypertrophy, how- 
ever, by raising the blood-pressure in the kidneys is supposed to 
counterbalance the renal deficiency, and even lead to an increase 



246 CLINICAL DIAGNOSIS. 

in the amount of urine. There seems to be some doubt as to the 
correctness of such an explanation, as the existence of hypertrophy 
of the left ventricle in the absence of glandular disease of the kid- 
neys by no means leads to a degree of polyuria at all comparable to 
that observed in this disease. It is possible that while cardiac hyper- 
trophy in itself may be one of the causative factors, still another 
may be a vicarious action of the sound glandular elements. If 
such be the correct explanation, the coexisting polydipsia is merely 
secondary. This, however, can be regarded only as an hypothesis, 
and the diminished renal secretion associated with a gradually de- 
veloping cardiac dilatation cannot be upheld as an absolute proof 
of its correctness. 

Polyuria, furthermore, has been observed in the most diverse dis- 
eases of the nervous system, both functional and organic, illustrating 
the influence of the nerve-centres upon renal activity, leaving the ulti- 
mate cause an open question. It is thus frequently observed both 
as a transitory and a permanent symptom in cases of hysteria. 
Large quantities of a very pale urine are secreted after the occur- 
rence of severe hysterical seizures, but the same may be observed 
throughout the course of the disease. A similar condition is fre- 
quently seen in neurasthenia, migraine, chorea, and epilepsy. 

On the whole, it may be said that a paroxysmal polyuria in 
nervous diseases is associated with functional derangements, while 
a continuous polyuria appears to be connected rather with true or- 
ganic changes. It has thus been observed in certain cases of tabes, 
cerebro-spinal and spinal meningitis, the first stage of general paresis, 
tumors affecting the medulla, the cerebellum, and spinal cord, in 
injuries aSecting the central nervous system, in Basedow's dis- 
ease, etc. 

Cases of idiopathic diabetes insipidus most probably must be classi- 
fied under this heading ; enormous quantities of urine may be secreted 
in this disease, being equalled only by cases of diabetes mellitus, and 
at times reaching 43 liters per diem. 

Oliguria. Oliguria is, on the whole, more frequent than polyuria, 
being met with in almost all conditions associated with a lowered 
blood-pressure. First in order stand those cases of cardiac disease in 
which compensation has failed, whether the cardiac weakness be pri- 
mary or occurring secondarily to other diseases ; i. e., pulmonary, 
hepatic, and renal. 

The oliguria observed in the so-called continuous fevers, notably 






THE URINE. 247 

typhoid fever, is probably also referable to the existence 1 of cardiac 
weakness. It should be remembered, however, that a larger propor- 
tion of water is eliminated through the skin and lungs than normally* 
and that a retention of fluids also undoubtedly occurs in fevers, not 
referable to cardiac weakness, while still other factors may be con- 
cerned in its production. 

The oliguria occurring in acute nephritis and in chronic paren- 
chymatous nephritis in all probability depends largely upon mechan- 
ical causes, the increased intra-canalicular resistance in the form of 
desquamated epithelium and tube-casts, as well as the pressure of the 
exudate upon the bloodvessels obstructing the passage of urine, while 
the functional activity of the diseased glandular elements is at the 
same time lowered. 

Upon mechanical causes, also, depend all those cases of oliguria 
associated with the presence of a stone or tumor, which pressing upon 
any part of the urinary tract impedes the flow of urine. Oliguria 
may occur as a nervous manifestation in connection with puerperal 
eclampsia, lead-colic, hysteria, psychic depressions, preceding and 
in the course of epileptic seizures. Whenever there is a diminu- 
tion in the amouut of bodily fluids oliguria is also observed, this 
being particularly marked in cholera and following severe hemor- 
rhages. 

Obstruction to the flow of blood in the vena cava or liver, leading 
to an increase of venous pressure and a decrease of arterial pressure 
in the kidneys, likewise results in oliguria, as is seen in atrophic 
hepatic cirrhosis, acute yellow atrophy, thrombosis of the vena cava 
and the renal vein, or in cases in which pressure is exerted upon 
these by tumors, ascitic fluid, etc. 

In any case the oliguria may go on to complete anuria, which 
latter condition not infrequently precedes death. Anuria may, how- 
ever, also occur independently of a pre-existing oliguria, notably so 
in cases of hysteria. 

Specific Gravity. 

The specific gravity of normal urine varies between 1.015 and 
1.025, corresponding to 1200 to 1500 c.c, the normal amount of 
urine voided in twenty-four hours. Pathologically a specific gravity 
of 1.002 on the one hand and 1.060 on the other may occur, depend- 
ing upon the amount of solids and fluids present, increasing as the 



948 CLINICAL DIAGNOSIS. 

solids increase, the amount of urine remaining the same, and decreas- 
ing as the amount of fluid increases, the solids remaining the same. 
The specific gravity is thus an index, in a general way, of the meta- 
bolic processes taking place in the body. 

The necessity of determining the specific gravity of the total 
amount of urine voided in a given case, and not that of an individual 
specimen passed during the twenty-four hours, becomes apparent 
upon considering the variations which can occur in the solids and 
liquids daring the day. The ingestion of large amounts of water 
or beer would, of course, result in the passage of a correspond- 
ingly large quantity of urine within the next few hours, containing 
but a small amount of solids, and hence presenting a low specific 
gravity. It would be erroneous to infer a diminished excretion 
of solids for the day from such an observation, as succeeding speci- 
mens would in all probability be passed presenting a higher spe- 
cific gravity. An observation, moreover, made upon a specimen 
taken from the collected quantity of urine of the twenty-four hours 
can only then convey a correct idea if the quantity falls within the 
normal limits. If this should not be the case, the volume of urine 
observed must first be reduced to the normal and the specific 
gravity then taken. 

Supposing a known quantity of common salt to be dissolved in 
1000 c.c. of water, so that the resulting specific gravity be 1.24, 
by doubling the amount of salt and water the specific gravity would 
still remain the same, while the amount of salt would actually be 
twice as large as at first. In order to obtain the specific gravity 
indicating the true amount of solids present it would be necessary 
to concentrate the fluid to 1000 c.c. The specific gravity being in- 
versely proportionate to the amount of fluid secreted, the necessary 
correction is made according to the following formula : 

S P- g r - = -L 

in which Sp. gr. indicates the specific gravity to be determined, q the 
amount of urine actually passed, d the specific gravity observed, and 
N the normal amount of urine — i.e., 1200 c.c. 

Example: A patient has passed 3000 c.c. of urine in the twenty- 
four hours with a specific gravity of 1.017 ; this is corrected accord- 
ing to the above formula: 

Sp . 3001X17 = j 

1 s 1200 



THE URINE. 249 

From the specific gravity the amount of solids can be calculated 
with sufficient accuracy for clinical purposes by multiplying the last 
two decimal points by 2, the number obtained indicating the amount 
of solids in 1000 c.c. of urine. 

To illustrate the necessity of either indicating the total amount 
of urine passed within twenty-four hours, and of taking the specific 
gravity from this collected urine, or of correcting the specific gravity 
as shown above (which latter method is far preferable, and should 
be generally adopted in urinary reports), the following case may 
be supposed : 

A " specimen " of urine is taken from a man, presenting a specific 
gravity of 1.002; by multiplying the 2 by 2, the person would be 
supposed to pass 4 grammes of solids in every 1000 c.c. of urine. 
Had the specific gravity been observed in the total amount of urine 
passed in the same twenty-four hours, it would have been found to 
be 1.012, the man having passed 3000 c.c. of urine; by multiplying 
12 by 2, 24 grammes of solids would have represented the amouut 
in every 1000 c.c; i. e., 24 X 3 = 72 grammes in toto. The same 
result would have been reached by correcting the specific gravity of 
1.012 for the normal amount of urine. 

The first calculation then would have indicated a considerable 
deficit as compared with the second. 

The following rules for practice may thus be stated: 

1. Whenever the specific gravity only is to be indicated in a urin- 
ary report it should always be the corrected one ; if this is not done, 
the amount of urine should be stated in every case. 

2. The specific gravity should always be taken from the collected 
urine of the twenty -four hours, and never from a specimen ad libitum. 

From the rule that the specific gravity of a urine is inversely pro- 
portionate to the amount of fluid eliminated it must follow that 
whatever causes produce oliguria will also produce a high specific 
gravity, while all those causes which will produce a polyuria will 
similarly produce a low specific gravity, with the following exceptions: 

1. A diminished amount of urine with a lowered specific gravity 
occurs in many chronic diseases, and toward the fatal termination of 
acute diseases, indicating a defective elimination of solids. 

2. The same may be observed in certain cases of oedema. 

3. Following copious diarrhoea, vomiting, and sweating. 

4. A high specific gravity is associated with polyuria in diabetes 
mellitus. 



250 



CLINICAL DIAGNOSIS. 



Fig. 73. 



Unfortunately the determination of the specific gravity and the 
solids contained in urines does not furnish as valuable information in 
many cases as would be a priori expected, organic constituents in 
general being possessed of a lower specific gravity than the inorganic, 
among which the chlorides are especially important, as they occur in 
considerable amount in normal urine. It thus not infrequently hap- 
pens that the nitrogenous constituents are considerably increased, while 
the specific gravity is relatively low, owing to the absence or a dimi- 
nution in the amount of chlorides. In 
other words, while the specific gravity 
may be regarded as a fair index of the 
total amount of solids excreted, its in- 
crease or decrease furnishes no informa- 
tion as to the nature of the constituents 
causing such a change. 

Determination of the Specific 
Gravity. The specific gravity of urine 

fis most conveniently determined by 
j 11 means of a hydrometer indicating de- 

grees varying from 1.002 to 1.040. 
Such instruments constructed especially 
for the examination of the urine are 
termed urinometers (Fig. 73). A good 
instrument should have a stem upon 
which the individual divisions are at 
least 1.5 mm. apart, and in which each 
division should correspond to a half de- 
gree. 

Urinometers may also be purchased 
which are provided with a thermometer, 
a matter of great convenience. Every 
instrument should be carefully tested by 
comparison with a standard hydrometer. 
In order to determine the specific grav- 
ity in a given case a cylindrical vessel is 
nearly filled with urine and the urin- 
ometer slowly inserted, the reading being taken at the lower meniscus 
by bringing the eye on a level with it as soon as it has come to a rest. 
Precautions. 1. The urinometer must be given ample room and 
the reading should never be taken when the urine adheres to the 




Urinometer. (W. Simon 



THE URINE. 



251 



sides of the vessel, as owing to capillary attraction it is otherwise 
raised, causing the reading to become too high. 

2. The instrument must be perfectly dry and clean before being 
used, and should never be allowed to "drop" into the urine, as 
otherwise, the weight of the instrument being increased by adhering 
drops of water, the reading becomes too low. 

3. Any foam upon the surface of the urine should first be 
removed by means of a piece of filter-paper, as it interferes 
with the accuracy of the reading ; bubbles of air adhering to the 
instrument, thereby raising it, should be carefully removed with a 
feather. 

4. The specific gravity should always be determined in specimens 
taken from the twenty-four-hour urine, and corrected according to 
the formula given above. 

5. If the quantity of urine is too small to determine its specific 
gravity with a urinometer, the following method may be advan- 
tageously employed : 

About 50 c.c. of urine are measured off, preferably by means of 
a burette, into a small bottle provided with a ground-glass stopper 

Fig. 74. 




The pyknometer. 



(Fig. 74), and accurately weighed. The weight of the urine divided 
by its volume gives the specific gravity, which must, however, be 
corrected for the temperature of the urine. If accuracy be required, 
such a correction should be made in every case, as the specific gravity 
increases or decreases by 1° for every 3° C. above or below the point 



252 



CLINICAL DIAGNOSIS. 



for which the instrument is registered, viz., 15° C. According to 
Bouchardat and Mercier, this method is not strictly accurate, and the 
following table has been constructed by which the proper corrections 
can readily be made : 



Tempera- 


Urine 


Glycosuric 


Tempera- 


Urine 


Glycosuric 


ture. 


normal. 


urine. 


ture. 


normal. 


urine. 





0.9 


1.3 


18 


0.3 


0.6 


1 


0.9 


1.3 


19 


0.5 


0.8 


2 


0.9 


1.3 


20 


0.9 


1.0 


3 


0.9 


1.3 


21 


0.9 


1.2 


4 


0.9 


1.3 


22 


1.1 


1.4 


5 


0.9 


1.3 


23 


1.3 


1.6 


6 


08 


1.2 


24 


1.5 


1.9 


7 


0.8 


1.1 


25 


1.7 


2.2 


8 


0.7 


1.0 


26 


2.0 


2.5 


9 


0.6 


0.9 


27 


2.3 


2.8 


10 


0.5 


0.8 


28 


2.5 


3.1 


11 


0.4 


0.7 


29 


2.7 


3.4 


12 


0.3 


0.6 


30 


3.0 


3.7 


13 


0.2 


0.4 


31 


3.3 


4.0 


14 


0.1 


0.2 


32 


3.6 


4.3 


15 


0.0 


0.0 


33 


3.9 


4.7 


16 


0.1 


0.2 


34 


4.2 


5.1 


17 


0.2 


0.4 


35 


4.6 


55 



Example : Supposing the specific gravity to have been 1.030 at 
a temperature of 20° C, it would be necessary to add 0.9 to the 
1.030, making this 1.0309; at a temperature of 10° C, it would 
similarly be necessary to subtract 0.5. 

Determination of the Solid Constituents. As indicated 
above, the amount of solids can be calculated with a sufficient degree 
of accuracy fcr clinical purposes by multiplying the last two decimal 
points of the specific gravity by 2, the number obtained indicating 
the amount of solids in every 1000 c.c. of urine. If greater accu- 
racy be required, the following method may be employed : 

Five c.c. of urine, accurately measured, are placed in a watch- 
crystal, containing a little dry sand (sand and crystal having been 
previously weighed) ; this is placed over a dish containing concen- 
trated sulphuric acid, and arranged under the receiver of an air- 
pump, which has been made perfectly air-tight by thoroughly lubri- 
cating the ground-glass edge of the bell with mutton tallow and 
applying the bell with a slightly grinding movement to the ground- 
glass plate. The receiver is now exhausted and the urine allowed to 



THE URINE. 



253 



remain in the vacuum for twenty-four hours, when the bell is again 
exhausted and left for twenty-four hours longer ; at the end of this 
time the crystal is weighed, the difference between the two weights 
obtained indicating the amount of solids in 5 c.c. of urine, from 
which the percentage and total amount are readily calculated. 

The slight loss of ammonia which results when this method is 
employed scarcely affects the accuracy of the result. 



REACTION. 

The reaction of the twenty-four-hour urine is, as a rule, acid ; 
individual specimens, passed in the course of twenty-four hours, 
may be either alkaline, acid, or amphoteric. 

When a mixture of several different acids is brought into contact 
with a mixture of alkalies, the acids combine with the alkalies accord- 
ing to the degree of affinity which exists between the two and the 
amount present of each. Upon the excess of acids over alkalies, and 
vice versa, depends the resulting reaction. If the alkalies are not 
sufficient in amount to saturate the acids, an acid reaction will result, 
while an insufficient amount of acid will give rise to an alkaline 
reaction. The same principle holds good for the acids and alkalies 
giving rise to the salts present in the urine. As here the alkaline 
substances are not present in sufficient amount to saturate the acids, 
which can readily be seen from the following table, the acid reaction 
of normal urine is explained : 



HC1 


S0 3 


PA 


K 


Na 


NH 3 


Ca 


Mg 


10.1265 
6.3811 


2.3157 
1.3315 


3.0334 

0.9827 


2.5830 
1.5194 


5.4780 
5.4780 


5977 

0.8087 


0.0405 
0.0233 


0.0880 
0.0843 



The figures in the first column indicate the average daily amount 
of the inorganic acids and alkalies present in the urine of twenty- 
four hours, and the figures in the second column their equivalents in 
terms of !Na, that of P 2 O s having been estimated as NaH 2 P0 4 . 
From this it is seen that the acid equivalents, 8.6953, exceed the alka- 
line equivalents, 7.9137, by 0.7816 gramme of Na. There are pres- 
ent then in the urine, in addition to the normal salts of the monobasic 
acids, acid salts and especially diacid sodium phosphate, NaH 2 P0 4 . 
To the latter the acidity of the urine has usually been attributed, 
but this statement is not strictly correct ; other salts, particularly the 



o 5 4 CLINICAL DIAGNOSIS. 

acid urate of sodium and the acid hippurate of sodium are probably 
also concerned in the production of the acid reaction of the urine. 
If, on the other hand, the alkalies exceed the acids in amount, an 
alkaline urine will result, which may occur physiologically under 
various conditions. 

The so-called amphoteric reaction may be observed at times when 
the diacid aud neutral sodium phosphates, XaILP0 4 and Xa 2 HP0 4 , 
are present in a certain definite proportion, the urine changing the 
color of red litmus-paper to blue, and vice versa. 

A neutral urine is never observed under normal conditions. More- 
over, the presence of a free acid is not possible, as it would immedi- 
ate! v cause the formation of ammonia from the tissues of the body, 
and, finally, any urea present in the urine would combine with any 
free acid which might be present. 

The question now arises, Whence does the acidity of the urine result, 
and what are the ultimate causes which will produce an alkaline and 
an amphoteric reaction ? 

These are problems which as yet await a final decision. Our pres- 
ent ideas, however, may be formulated as follows : In the metabo- 
lism of the body-tissues acids are constantly produced, chief among 
these being sulphuric acid, resulting from albuminous decomposition, 
and hydrochloric acid, which at a certain period of digestion is re- 
absorbed into the blood together with peptones. As the alkalinity of 
the blood is due to neutral sodium phosphate and sodium carbonate, 
these salts are attacked by the free acids as soon as they enter the blood, 
the result being the formation of acid salts, and as the latter diffuse 
more readily through an animal membrane than alkaline salts, the se- 
cretion of an acid urine from the alkaline blood is in part explained. 

Nevertheless, it is impossible to exclude a certain specific action 
on the part of the glandular elements of the kidneys, as otherwise 
the secretion of all glands, supposing this to depend upon a process 
of filtration or diffusion only, would necessarily be acid. 

As the alkalinity of the blood increases the acidity of the urine 
decreases, uutil finally an alkaline urine results. The degree of the 
alkalinity of the blood, however, depends essentially upon the 
nature of the food and the secretion of the gastric juice, viz., hydro- 
chloric acid. The ingestion of vegetable food rich in salts cf 
organic acids, which become oxidized iu the body to the carbonates of 
the alkalies, will result in the passage of an alkaline urine, as the 
alkalies thus formed when absorbed into the blood are more than 



THE URINE. 255 

sufficient to neutralize completely all the acids present, the elimina- 
tion of neutral sodium phosphate alone taking place. In the case 
01 animal food the reverse holds good. The alkaline carbonates here 
formed not being sufficient to neutralize the excess of acids, diacid 
phosphate of sodium is eliminated in large quantity. 

An amphoteric urine results whenever the elimination of neutral 
and acid sodium phosphate is equal ; such an occurrence must, there- 
fore, be regarded as being more or less an accident. 

As the alkalinity of the blood is increased during the secretion of 
the acid gastric juice, it may frequently happen, especially following 
the ingestion of a large amount of food, that an alkaline urine is 
voided. If this does not take place, the acidity of the urine is at 
least diminished, to increase again during the process of resorption 
of hydrochloric acid and peptones. The statement so generally 
made in text-books that the urine secreted after a meal is alkaliue 
is not strictly correct ; in a series of observations made by the 
author upon human subjects an alkaline urine was observed in only 
20 per cent, of the cases examined. 

It may then be stated that an alkaline uriue will result under 
physiologic conditions whenever the alkaline salts present in the 
food are sufficient to neutralize all the acids formed, as occurs in the 
case of a vegetable diet, and, furthermore, whenever the period of 
gastric secretion is lengthened. 

If an acid urine be allowed to stand exposed to the air for a certain 
length of time, its degree of acidity gradually diminishes, the reaction 
finally becoming alkaline. At the same time the urine becomes cloudy 
and deposits a sediment, consisting of ammonio-magnesium phos- 
phate, MgNH 4 P0 4 -f-6H 2 0, neutral calcium phosphate, Ca 3 (P0 4 ) 2 , 
and still later of ammonium urate, C 5 H 2 (NH 4 ) 2 ]N~ 4 03, in addition to 
the constituents of the primitive nubecula — i. e., a few mucous cor- 
puscles and pavement epithelial cells. The entire volume of urine, 
moreover, remains cloudy, owing to the presence of innumerable 
bacteria. The odor becomes extremely disagreeable, and has been 
termed " urinous. n In short, " ammoniacal decomposition" has 
occurred. This has been shown to depend upon the action of certain 
bacteria, notably the micrococcus ureas and the bacterium ureas, present 
in the air, these organisms causing the decomposition of the urea 
found in every urine, with the formation of ammonium carbonate, 
according to the following equation : 

C(HNH 3 ) a + H 2 = (NH 4 ) a C0 3 

(XH 4 ) 2 C0 3 = 2NH 3 + H 2 + CO, 



256 CLINICAL DIAGNOSIS. 

Here as elsewhere, however, it is not the bacterium which directly 
produces the result, but a bacterial product, and in this case an 
enzyme. 

An alkaline urine, the alkalinity, however, not being due to am- 
moniacal fermentation, but to causes already mentioned, may, of course, 
undergo the same change as an acid urine; but it is necessary to 
distinguish sharply between these two varieties of alkaline urines, 
the recognition of the cause of the alkalinity being very often most 
important in diagnosis. The distinction is readily made by fasten- 
ing a piece of sensitive red litmus-paper in the cork of the bottle 
containing the urine. If the alkalinity of the urine be due to 
the presence of ammonia, the litmus-paper will turn blue, but soon 
changes to red again when exposed to the air; while a urine, the 
alkalinity of which is due to the presence of fixed alkalies, will turn 
red litmus-paper blue only when immersed directly in the urine, the 
change in color at the same time persisting. 

As ammoniacal decomposition can also occur within the urinary 
passages, it is important whenever an alkaline reaction referable to 
the presence of ammonia is observed to test the urine at once upon 
being voided, or, still better, to procure a portion with the catheter. 
Such urines are frequently seen in cases of cystitis the result of 
paralysis, urethral stricture, gonorrhoea, etc. 

An intensely acid reaction is observed in almost all concentrated 
urines, especially in fevers, in certain diseases of the stomach asso- 
ciated with a diminished or suspended secretion of hydrochloric acid, 
in gout, lithiasis, acute articular rheumatism, chronic Bright's dis- 
ease, diabetes, leukaemia, scurvy, etc. Whenever a very acid urine 
is secreted for a considerable length of time the possibility of renal 
irritation and the formation of concretions should be borne in 
mind. 

An alkaline urine, the alkalinity of which is not owing to the 
presence of ammonia, but to a fixed alkali, is observed in certain 
cases of debility, especially in the various forms of ansemia, follow- 
ing the resorption of alkaline transudates, the transfusion of blood, 
frequent vomiting, a prolonged cold bath, etc. It may also be due 
to the ingestion of certain medicines, viz., salts of the organic aids 
and alkaline carbonates, the former being transformed into the latter, 
as has been mentioned. An increase in the degree of acidity may 
similarly take place after the ingestion of mineral acids. 

It is apparent then that an increase or a decrease in the acidity of 



THE URINE. 257 

the urine cannot be immediately attributed to a certain disease. 
Conclusions can only be drawn, if all other causes, both physiologic 
and pathologic, can be eliminated. 

Determination of the Acidity of the Urine. One hundred 
c.c. of urine taken from the total amount voided in twenty-four 
hours are titrated with a one-tenth normal solution of sodium hy- 
drate, using a delicate litmus-paper as an indicator, until a faintly 
alkaline reaction is produced. 1 As 40 parts by weight of sodium 
hydrate combine with 63 parts by weight of oxalic acid, according 
to the equation : 

C 2 H 2 4 -f 2NaOH = C 2 Na 2 4 + H 2 0, 

it is apparent that 1 c.c. of the decinormal solution of sodium 
hydrate containing 0.004 gramme of the substance will represent 
0.0063 gramme of oxalic acid. The number of c.c. of the one- 
tenth normal solution employed multiplied by 0.0063 will, there- 
fore, give the percentage-acidity of the urine in terms of oxalic acid. 
The total acidity of the urine thus determined corresponds to from 
2 to 4 grammes of oxalic acid per diem. 

Instead of using litmus as an indicator, phenolphthalein may be 
employed, one or two drops of a 1 per cent, alcoholic solution being 
added to 100 c.c. of urine which has been previously decolorized by 
filtration through neutral animal charcoal. In this case it is neces- 
sary to add a slightly larger amount of the one-tenth normal solution 
in order to bring about the end-reaction. This is probably owing to 
the fact that the carbonic acid of the urine responds more intensely 
to phenolphthalein than to litmus. 

Unfortunately the method is not strictly accurate, owing to the 
action of the alkali employed upon the acid sodium phosphate, a 
mixture of neutral and acid sodium phosphates resulting at first, 
which produces the so-called amphoteric reaction and renders the 
recognition of the true end-reaction impossible. A slight excess of 
NaOH must, therefore, be added and the reading taken when the 
reaction has become faintly alkaline, the degree of acidity found being 
a trifle too high. 

An increase in the acidity of the urine upon standing has been 
repeatedly observed, and is probably due to the formation of new 
acids from pre-existing acid-yielding substances, such as certain 

1 The urine is carefully guarded against ammoniacal decomposition by the addition to the 
first portion voided of from 20 to 25 c.c. of a solution of 10 grammes of oil of peppermint in 100 
c.c. of alcohol. 

17 



9.58 CLINICAL DIAGNOSIS. 

carbohydrates, alcohol, etc., which have undergone fermentation. 
This phenomenon is frequently observed in the urine of diabetic 
patients. 

A decrease in the acidity of normal urine upon standing is. on 
the other hand, the rule, owing to decomposition of urate of sodium 
by the acid phosphate of sodium, acid urate of sodium and later on 
uric acid resulting, which are thrown down as a sediment in conse- 
quence of the diminished acidity of the urine, and which, hence, no 
longer influence its reaction. This is shown in the equations : 

I. ]SaH 2 P0 4 -j- C.H.Na^Os = ya : HP0 4 — OHA'a^Os 
II. ^aH^PO, — C 5 H 3 ":SaXo 3 = y a , ; HP0 4 - C 5 H^A 

THE CHEMISTRY OF THE URINE. 

General Chemical Composition of the Urine. It has been 
pointed out that owing to the influence exerted upon the chemical 
composition of the nrine by many factors, such as age, sex. temper- 
ature, digestion, exercise, etc., the figures given by different observers 
to express the absolute quantities of the various ingredients eliminated 
in the twenty-four hours vary within fairly wide limits. A general 
idea may, however, be formed of these constituents and their average 
amounts under physiologic conditions from the following table : 

Composition of Noemal Himax Crete of Average Specific 
Geavity. I f.. 1.02(1 : 

Per liter. Per 24 hours. 

Water 956 grnis. 1248 gi 

Organic matter . . . 28-3€ " 36-38 

Urea 25.87 " ) " 

Uric acid 0.40 grin. 0.52 grin. 

Hippuric acid .... 0." .65 " 

-atin aDd creatinin . . 0.8( 1.0 " 

Xanthin bases .... 0.04 u 

C loring-rnatter and extractive? 4.5 grins. 5.850 grnis. 

Volatile fatty acids . 

Oxalic acid 

Phenol snlpkate 

Indoxyl and skatoxyl sulphate | 

Paraoxyphenylacetic acid . j- Very little. 

Sugar .... 

Mucus, pepsin . 

Fatty acids . . . . | 

Glycerine-phosphoric acid . J 

1 Taken from Gautier. 





THE 


UBINR 




Mineral matter . 




10-17 grins. 


20 21 grms 


Sodium chloride 




10.5 " 


13.65 " 


Alkaline sulphates . 




3.1 " 


4.03 " 


Earthy phosphates . 




0.7G grin. 


0.08 grm. 


Alkaline phosphates 




1.43 " 


1.86 " 


Silicic acid . 




• ) 




Nitric acid . 




. >■ Traces. 




Gases (0, CO a , N) 




. ) 





259 



In pathologic conditions the following substances may also be 
found in solution : Albumin, globulin, hemialbumose, peptone, mucin 
(nucleo-albumin), glucose, lactose, inosit, dextrin, biliary constituents, 
viz., bile-acids and bile-pigments, blood-pigment, urorubrohsematin, 
urorubrofuscin, melanin, leucin, tyrosin, oxybutyric acid, allantoin, 
fat, lecithin, cholesterin, acetone, alcohol, Baumstark's substance, 
urocaninic acid, cystin, and sulphuretted hydrogen. 

Quantitative Estimation of the Mineral Ash of the Urine. 
In order to^estimate the amount of mineral ash in the urine the fol- 
lowing method may be employed : 

Fifty c.c. of urine are evaporated to dryness in a weighed porce- 
lain dish at a temperature of 100° C, then, covered, over the free 
flame until gases cease to be evolved, care being taken not to 
heat too strongly in order to prevent sputtering. The residue is 

Fig. 75. 




Desiccator. (W. Simon.) 



taken up with distilled boiling water, and, after standing, filtered 
through a Schleich and SchulFs filter, the weight of the ash con- 
tained in this being known. The dish, as also the contents of the 
filter/are well washed with hot water. Filtrate and washings are set 
aside and the dish and filter dried in the oven at 115° C. The filter 



260 CLINICAL DIAGNOSIS. 

is now placed in the dish and slowly incinerated. As soon as the ash 
has turned white the filtrate and washings are placed in the same 
dish, evaporated at 100° C, and then carefully heated over the free 
flame. Upon cooling in the desiccator (Fig. 75) the dish with its 
contents is weighed, the difference between its present and previous 
weight indicating the quantity of ash contained in 50 c.c. of urine. 

Precautions : 1. Care should be taken to allow the dish to become 
faintly red only for a moment, since some of the chlorine is otherwise 
volatilized. Some phosphoric acid also may be volatilized, and too 
strong a heat, moreover, may cause the transformation of sulphates into 
sulphides, the organic material present acting as a reducing agent. 

2. If the organic ash is not completely incinerated, it is best to 
allow the dish to cool and then to moisten the ash with a few drops 
of distilled water, it being thereby brought into closer contact with 
the surface of the dish. 

The Chlorides. 

The chlorides excreted in the urine are derived from the food. As 
they are thus present in a much larger amount than all other inor- 
ganic salts combined, and in quantity more than sufficient to supply 
the needs of the body-economy, the relatively large amount of chlo- 
rides found in the urine under physiologic conditions, as compared 
with the other inorganic constituents, is readily explained. 

Of the alkalies in the urine, sodium in combination with chlorine 
exists in greatest amount, and for clinical purposes it is most con- 
venient to calculate the total quantity of chlorides found in terms of 
sodium chloride ; a small proportion of chlorine also occurs combined 
with potassium, ammonium, calcium, and magnesium. 

From 11 to 15 grammes of sodium chloride, representing the total 
quantity of chlorine, are normally eliminated in the twenty-four 
hours, the amount depending, of course, directly upon that con- 
tained in the food ingested. If the amount of nourishment is 
diminished, a decrease in the elimination of the chlorides is observed. 
If this be carried to the point of starvation, the chlorides disap- 
pear almost entirely from the urine, the traces remaining being de- 
rived from the bodily fluids. The latter retain tenaciously a certain 
amount, which differs but slightly from that normally present. If 
at this stage food containing sodium chloride is again taken, a portion 
will be retained in the body until the original equilibrium is restored. 
A similar retention may be observed for a few days following the 






THE URINE. 261 



ingestion of large quantities of water, which causes an increased 
elimination of chlorides. 

This tenacity on the part of the body in retaining sodium chloride 
is strikingly seen when the potassium salt is substituted for the 
sodium salt ; in this case the amount of the sodium in the serum of 
the blood will be found to vary but very slightly. 

At the same time it has been shown that the excretion of sodium 
chloride can be very materially increased by the ingestion of potas- 
sium salts, notably the neutral potassium phosphate (Iv 2 HP0 4 ). This 
has been supposed to act upon the sodium chloride present in the 
serum, causing the formation of potassium chloride and neutral 
sodium phosphate, which are both eliminated from the body as for- 
eign material ; a point is finally reached, however, when the sodium 
chloride ceases to be excreted. 

This provision of the economy, in virtue of which an increase in 
the elimination of the salt is followed by its retention, and a pre- 
vious retention by an increased elimination, is supposed to be refer- 
able to the albuminous metabolism taking place in the body. It 
may be stated, as a general rule, that any increase in the amount 
of circulating albumin will be followed by an elimination of chlo- 
rides, these having been previously retained by the albuminous bodies 
in consequence of the great affinity which exists between them. 
At the same time the elimination of chlorides is also influenced by 
the quantity of urine excreted, increasing and decreasing with its 
volume. 

Pathologically the excretion of the chlorides may vary within 
wide limits, diminishing on the one hand to zero, and increasing on 
' the other to as much as 50 grammes or more in the twenty-four hours. 
A marked diminution, going on in some cases to a total absence of 
the chlorides, was formerly thought to be pathognomonic of acute 
croupous pneumonia. Recent investigations, however, have shown 
that such a condition is present to a greater or less degree in most 
acute febrile diseases, such as scarlatina, roseola, variola, typhus and 
typhoid fevers, recurrens, and acute yellow atrophy. 

The explanation of this phenomenon must be sought for, first, in 
a diminished ingestion of chlorides ; second, in a retention of these 
in the blood, probably associated with an increase in the amount of 
circulating albumin ; third, in a diminished renal secretion of water ; 
fourth, in a possible elimination of a portion of the chlorides from 
the blood by other channels, as in cases of severe diarrhoea, the for- 



262 CLINICAL DIAGNOSIS. 

mation of serous exudates, etc. Intermittent fever appears to form 
an exception to this rule ; the chlorides, it is true, are usually dimin- 
ished, but not to the extent seen in the other diseases mentioned ; 
they have, moreover, been found to increase during and sometimes 
immediately after a paroxysm, this increase being, of course, followed 
by a corresponding decrease. 

The chlorides are diminished in all acute and chronic renal diseases 
associated with albuminuria, owing to some extent, at least, to a 
diminished secretion of water. In all cases of carcinoma of the 
stomach, chronic hypersecretion of gastric juice, associated with dila- 
tation, a decrease is also observed, which in certain cases of hyper- 
secretion and hyperacidity the result of gastric ulcer may go on to 
a total absence. In ansemic conditions the chlorides are likewise 
diminished, as also in rickets. In melancholia and idiocy a striking 
decrease is observed ; in dementia, chorea, and pseudo-hypertrophic 
paralysis this is less marked. A total absence has been noted in 
pemphigus foliaceus, and a considerable diminution in the beginning 
of impetigo, as also in chronic lead-poisoning. 

The chlorides are found in increased amount, on the other hand, 
in all conditions in which retention has previously occurred, chief 
among these being the acute febrile diseases and cases in which a 
resorption of exudates and transudates, associated with an increased 
diuresis, is taking place. A marked increase has also been noted in 
some cases of diabetes insipidus, in which 29 grammes of sodium 
chloride have been eliminated in the twenty-four hours. A similar 
increase may occur in prurigo, in which, in one instance, 29.6 grammes 
were passed in twenty-four hours. In cases of general paralysis 
during the first stage an increased elimination goes hand in hand 
with an increased ingestion of food. In epilepsy the polyuria fol- 
lowing the attacks is associated with an increase in the chlorides. 

Of drugs, certain diuretics, and some of the potassium salts, as 
has been mentioned, produce an increase : the chlorine contained in 
chloroform, whether administered internally or as an anaesthetic, is 
in part excreted in the form of a chloride. Salicylic acid, on the 
other hand, is said to cause a temporary diminution. 

It is of practical importance to note that in acute febrile diseases 
the diminution in the chlorides appears to vary with the intensity 
of the disease, a decrease to 0.05 gramme pro die justifying the 
conclusion that the case under observation is of extreme gravity. 



THE URINE. 263 

It may at times also indicate the previous occurrence of severe diar- 
rhoea, or the formation of exudates of considerable extent. 

A continued increase in the course of the disease will inversely- 
lead to the conclusion that the patient's condition is improving. The 
elimination of the chlorides at the same time furnishes a fair index to 
the digestive powers of the patient. This rule also holds good for 
most chronic diseases. All other causes which might lead to an 
increase or decrease being eliminated, an excretion of from 10 to 15 
grammes indicates a fair condition of the appetite and a normal 
digestive power, a decrease being associated with the reverse. 

Au increased elimination of chlorides occurring in cases of oedema, 
and associated with the existence of serous exudates, is always of 
good prognostic significance, pointing to a resorption of the fluid. 

A continued elimination of more than 15 to 20 grammes, all other 
causes producing such an increase being excluded, may be considered 
as pathognomonic of diabetes insipidus. 

Test for Chlorides in the Urine. The recognition of the chlo- 
rides in the urine is based upon the fact that the addition of a solu- 
tion of nitrate of silver causes their precipitation, the reaction taking 
place according to the following equation : 

AgN0 3 + NaCl = AgCl + NaN0 3 . 

Silver chloride thus formed is insoluble in nitric acid. 

The test is made in the following manner : After having removed 
any albumin that may be present, according to methods given else- 
where (see Alburmn), a few c.c. of urine are acidified in a test-tube 
with about 10 drops of pure nitric acid, and a few c.c. of silver 
nitrate solution (1 : 20) added. The occurrence of a white pre- 
cipitate indicates the presence of chlorides. An idea may be formed 
at the time as to the quantity present, the occurrence of a heavy 
caseous precipitate pointing to a large amount. 

Quantitative Estimation of the Chlorides by the Method 
of Salkowsky-Volhard. When a solution of silver nitrate, acid- 
ified with nitric acid, is treated with a solution of potassium sulpho- 
cyanide or ammonium sulpho-cyanide in the presence of a ferric salt, 
the potassium sulpho-cyanide first causes the precipitation of white 
silver sulpho-cyanide, which, like silver chloride, is insoluble in 
nitric acid : 

AgN0 3 + KSCN = AgSCN + KN0 3 . 

As soon as every trace of silver is precipitated it combines with 



264 CLINICAL DIAGNOSIS. 

the ferric salt to form iron sulpho-cyanide, which is of a blood-red 
color, according to the equation : 

6KSCN + Fe 2 (S0 4 ) 3 = Fe 2 (SCN) 6 + K 2 S0 4 . 

If the potassium sulpho-cyanide solution be of known strength, 
it is possible to estimate accurately the amount of silver present in 
the solution, the ferric salt serving as an indicator of the end of the 
reaction between the silver and the potassium sulpho-cyanide. 

Application to the urine : To urine which has been acidified with 
nitric acid an excess of a silver solution of known strength is added, 
and the silver not used in the precipitation of the chlorides then 
estimated according to the method given above. The difference be- 
tween the quantity thus found and the total amount used will 
be that consumed in the precipitation of chlorides, from which, 
knowing the strength of the silver solution, its equivalent in terms 
of sodium chloride is readily determined. 

Keagents necessary : 

1. A solution of silver nitrate of such strength that every c.c. 
corresponds to 0.01 gramme of sodium chloride. 

2. A solution of potassium sulpho-cyanide of such strength that 
25 c.c. correspond to 10 c.c. of the silver nitrate solution. 

3. A solution of a ferric salt saturated at an ordinary tempera- 
ture, such as ammonio-ferric alum. 

4. Nitric acid (specific gravity 1.2). 
Preparation of these solutions : 

1. As pointed out, the silver nitrate solution is made of such 
strength that every c.c. corresponds to 0.01 gramme of NaCl ; in 
other words, a standard solution is employed. 

The silver nitrate to be used for this purpose must be pure, the 
crystallized salt being used and not the sticks wrapped in paper, 
which latter always contain reduced silver. In order to test the 
purity of the salt, about 1 gramme is dissolved in distilled water, 
heated to the boiling-point, the silver precipitated by dilute muriatic 
acid and filtered off. The filtrate when evaporated in a platinum 
crucible should leave either no residue at all or only a very faint 
one; otherwise it is necessary to recrystallize the salt and test 
again, until the desired degree of purity is obtained. 

The determination of the quantity to be dissolved in 1000 c.c. of 
water is based upon the fact that one molecule of silver nitrate (molec- 
ular weight 170) combines with one molecule of sodium chloride 
(molecular weight 58.5) to form silver chloride and sodium nitrate. 



1HE URINE. 265 

As the solution of nitrate of silver shall be of such strength that 
1 c.c. corresponds to 0.01 grin, of NaCl, or 1000 c.c. to 10 grins., 
the quantity to be dissolved in 100 c.c. is found according to the fol- 
lowing equation : 

58.5 : 170 : : 10 : x ; 58.5 x = 1700 ; x = 29.059. 

Theoretically then this quantity should be dissolved in 1000 c.c. 
of water. It is better, however, to dissolve this in a quantity some- 
what less than 1000 c.c, such as 900 or 950 c.c, as the silver salt 
may contain some water of crystallization and the weighed-off quan- 
tity not represent the accurate amount required, but less, the correct- 
ing of a solution which is too strong being a much simpler matter 
than that of a solution which is too weak. 

To make this correction, or, in other words, to bring the solution 
to its proper strength, 0.15 gramme of sodium chloride which has 
been previously dried carefully by heating in a platinum crucible, is 
accurately weighed off, dissolved in a little distilled water, and further 
diluted to about 100 c.c To this solution a few drops of a solution 
of chromate of potassium are added, and the mixture titrated with 
that of silver nitrate. 

The nitrate of silver will first precipitate every trace of sodium 
chloride present, and then combine with the potassium chromate, 
forming red silver chromate, according to the equation : 

2AgNU 3 + K 2 Cr0 4 = Ag 2 CrO, + 2KN0 3 . 

The slightest orange tinge remaining after stirring indicates the end 
of the reaction. Were the solution of silver nitrate of the proper 
strength, exactly 15 c.c should have been used, as every c.c is to 
represent 0.01 gramme of NaCl. As a matter of fact, less will in 
all probability be needed, the solution having been purposely made 
too strong. Its correction then becomes a simple matter, it merely 
being necessary to determine the degree of dilution required. 

Supposing the 29.059 grammes of silver nitrate to have been dis- 
solved in 900 c.c. of water, and that 14.5 c.c instead of 15 c.c had 
been required to precipitate the 0.15 gramme of sodium chloride, it 
is evident that every 14.5 c.c of the remaining solution must be 
diluted w r ith 0.5 c.c. of water. It is, hence, only necessary to divide 
the number of c.c of the silver nitrate solution remaining by 14.5; 
the result multiplied by 0.5 represents the amount of water which 
must be added in order to bring the solution to the required strength. 



266 CLINICAL DIAGNOSIS. 

Hence the rule for the correction of a solution which has been found 
too strong : 

n 
in which C represents the number of c.c. which must be added to the 
solution remaining; N" the total number of c.c. remaining after 
titration; n the number of c.c. consumed in one titration; and d the 
difference between the number of c.c. theoretically required and that 
actually used in one titration. 

In the example given the equation would then read : 

/~i Job.oXO.o 09 90 

14.5 
32.29 c.c. of distilled water are added to the remaining 936.5 c.c., 
and the strength of the solution tested by a second titration. If the 
solution be found too weak, it is best to make it too strong and then 
to correct, as described. 

2. Preparation of the potassium sulpho-cyanide solution : From 
the equation AgNO s + KSCN = AgSCN + KNO s , it is seen that 
one molecule of silver nitrate (molecular weight 170) combines with 
one molecule of potassium sulpho-cyanide (molecular weight 97). 
The quantity of the latter to be dissolved in 1000 c.c. of water is 
thus found from the following equation : 

170:97 :: 11.6236 :x; 170 x = 11.6236 X 97; x=6.6. 

As potassium sulpho-cyanide is extremely hygroscopic, a solution 
is made which is too strong by dissolving about 10 grammes of the 
salt in 900 c.c. of distilled water. In order to bring this solution 
to its proper strength, 10 c.c. of the silver nitrate solution are 
diluted to 100 c.c, 4 c.c. of nitric acid (specific gravity 1.2) and 5 
c.c. of the ammonio-ferric alum solution added, and the mixture 
titrated with the KSCN solution ; the end-reaction is recognized by 
the production of a slightly reddish color, which persists on stirring. 
The KSCN solution having been purposely made too strong, it will 
be found that less than 25 c.c. will be needed in order to precipitate 
all the silver present. The quantity of water necessary for dilution 
is ascertained as above according to the formula : 

n 

3. The solution of ammonio-ferric alum is a solution saturated at 
ordinary temperatures, care being taken to insure the absence of 



THE URINE. 267 

chlorides in the salt, which may be effected, if necessary, by reerys- 
tallization. 

Method as applied to the urine: 10 c.c. of urine are placed in a 
small stoppered flask bearing a 100 c.c. mark, diluted with 50 c.c. 
of distilled water, and acidified with 4 c.c. of nitric acid. From a 
Mohr's burette 15 c.c. of the standard solution of silver nitrate are 
added. The mixture is thoroughly agitated and diluted with distilled 
water to the 100 c.c. mark. The silver chloride formed is filtered 
off through a dry folded filter into a dry graduate ; 80 c.c. of the 
filtrate are placed in a beaker, and, after the addition of 5 c.c. of the 
ammonio-ferric alum solution, titrated with the potassium sulpho- 
cyanide solution until the end-reaction — i. e., a slightly reddish tinge 
— is seen. If necessary, two such titrations should be made, the potas- 
sium sulpho-cyanide solution being added 1 c.c. at a time in the first, 
while in the second the total number of c.c. needed to bring about 
the end-reaction, less 1 c.c, are added at once, and then one-tenth of 
a c.c. at a time. 

The amount of chlorides present in the urine is calculated as 
follows : 

Example: Total quantity of urine 600 c.c; 6.5 c.c/of the potas- 
sium sulpho-cyanide solution were required to bring about the end- 
reaction in 80 c.c. of the filtrate ; this would correspond to 8.125 
c.c for the total 100 c.c. of filtrate, representing 10 c.c of urine, 
as is seen from the equation : 

n : 80 : : x : 100, 80 x = 100 n, x = 10 °- = -5- , 

80 4 

in which x represents the number of c.c. corresponding to 100 c.c 
of the filtrate, and n the number of c.c. actually used. 

These 8.125 c.c were used in precipitating the remaining c.c. of 
the silver nitrate solution not decomposed by the chlorides. As 25 
c.c of the potassium sulpho-cyanide solution correspond to 10 c.c. 
of the silver nitrate solution, the excess of silver solution in c.c is 
found from the equation : 

25 : 10 : : N : x, 25 x = 10 K x = l 01 ^ ^N 

25 5 

in which x represents the excess of silver nitrate solution in c.c, 
N that of the KSCN solution, as found in the equation above, x in 
this case being 3.25 c.c 



268 CLINICAL DIAGNOSIS. 

The difference between the total amount of silver solution em- 
ployed {i.e., 15 c.c.) and the excess {i.e., 3.25 c.c.) indicates, of 
course, the number of c.c. necessary for the precipitation of the chlo- 
rides in 10 c.c. of urine. In the case under consideration 11.75 c.c. 
were employed. As 1 c.c. of the silver solution represents 0.01 
gramme of NaCI, there must have been present in the 10 c.c. of 
urine 0.1175 gramme ; in 100 c.c. hence, 1.175 grammes, and in 
the total amount — i. e., 600 c.c. of urine — 7.05 grammes. 

From these considerations the following short rule results : Instead 
of first multiplying the number of c.c. of the potassium sulpho- 
cyanide solution corresponding to 80 c.c. of the filtrate by -|, as 
seen from the equation above, and the result by f, in order to find 
the number of c.c. of the potassium sulpho-cyanide solution repre- 
senting the excess of silver nitrate in 100 c.c. of the filtrate, and 
then deducting the result from 15, it is simpler to multiply by \ 
directly and deduct the result from 15, the number of grammes of 
sodium chloride contained in 1000 c.c. of urine being thus found. 
This figure is then corrected for the total amount of urine. 

Hence the equations, I., x = 15 — - ; II., 1000 : x : : A : Ch, or 

the combined formula Ch = - — -, 

1000 

in which Ch represents the quantity of chlorides contained in the 
total amount of urine, A the amount of urine actually passed, n 
the number of c.c. of the KSCN solution used in the precipitation 
of the excess of chlorides in 80 c.c. of the filtrate. 

So in the above case Ch = 600 ' """"*") = 7.05. 

1000 

The method described may be employed in the presence of albumin, 
albumoses, peptones, and sugar ; the urine, however, must be fresh, 
so as to insure the absence of nitrous acid. 

Direct Method. If absolute accuracy is not required, the follow- 
ing method may be employed : 

Ten c.c. of urine are diluted with distilled water to 100 c.c. and 
treated with a few drops of a solution of potassium chromate. This 
mixture is titrated with a one-tenth normal solution of silver nitrate 
until the end-reaction — i. e., the occurrence of a faint orange tinge, 
which no longer disappears on stirring — is reached. The number of 



THE URINE. 2G9 

c.c. used multiplied by 0.01 will indicate the amount oi chlorides 
present in 10 c.e. oi' urine. 

As uric acid, the xanthine bases, hypo-sulphites, sulpho-cyauides, 
and pigments are also precipitated by the silver nitrate, the end- 
reaction is delayed ; moreover, unless the urine be very pale, its 
recognition may be very difficult, and the error thus caused quite 
considerable. This is especially true oi* febrile urines which contain 
only a small amount oi' chlorides. 

Should iodides or bromides have been taken, these must first be 
removed, as the iodide and bromide oi silver, which are insoluble in 
nitric acid, would give too high a value. 

To this end the following method, which is a very accurate one, 
should be employed, its only disadvantage being the amount of time 
required. 

Estimation of the Chlorides after Incineration (according to 
Neubauer and Salkowsky). The principle of this method is the 
destruction of all organic material and the subsequent estimation of 
the chlorides contained in the mineral ash, by one of the methods de- 
scribed. 10 c.c. of urine are evaporated to dryness in a platinum 
crucible at a temperature slightly below 100° C, after the addition 
of pure, dried carbonate of sodium and from 3 to 5 grammes of potas- 
sium nitrate. The addition of the carbonate of sodium serves the 
purpose of transforming any ammonium chloride which may be 
present into sodium chloride ; the potassium nitrate used merely acts 
as an oxidizing agent. The residue is now carefully heated at a 
moderate temperature, allowed to cool, dissolved in distilled water, 
and accurately neutralized with very dilute nitric acid. In this solu- 
tion the chlorides are estimated most conveniently according to the 
second method. 

Should iodides or bromides be present, the aqueous solution just 
referred to is acidified with hydrochloric acid and the iodine and bro- 
mine thereby liberated extracted with carbon disulphide. As complete 
removal of these bodies is, however, only possible in the presence 
of a nitrite, it is better not to rely upon the presence of any that 
may have been formed during the process of incineration, but to add 
a few drops of a solution of potassium nitrite. After extraction the 
nitrous acid is decomposed by the addition of a little urea. The solu- 
tion is then neutralized with sodium carbonate ; should it be alkaline, 
dilute acetic acid is added until neutral. In this solution the chlo- 
rides are most conveniently estimated according to the second method. 



270 CLINICAL DIAGNOSIS. 

Albumin and sugar, if present, should be removed before the addi- 
tion of the sodium carbonate and potassium nitrate, if this method 
is employed, so as to obviate losses from sputtering, which would 
otherwise occur. Nitrous acid must also be removed for reasons 
given above. 

The Phosphates. 

The phosphates occurring in the urine are sodium, potassium, cal- 
cium, and magnesium salts of the tribasic acid H 3 P0 4 , the most 
important of which, as was pointed out in the chapter on Reaction, 
is the diacid sodium phosphate NaH 2 P0 4 , to which the acidity of 
the urine is to a large extent due. It is owing to the presence of 
this salt in the urine that the calcium phosphate is held in solution ; 
the fact, at least, that calcium and magnesium phosphates are thrown 
down when the urine is neutralized would point to this conclusion. 

The composition of the phosphates is liable to considerable varia- 
tion, depending upon the degree of acidity of the urine. As would 
be expected, diacid sodium phosphate and diacid calcium phosphate 
are present in an acid urine; in an amphoteric urine in addition to these 
there are to be found disodium phosphate, monocalcium phosphate, 
and monomagnesium phosphate, while in an alkaline urine trisodic 
phosphate, neutral calcium phosphate, and neutral magnesium phos- 
phate may be present. 

The alkaline phosphates normally exceed the earthy phosphates by 
one-third, and sodium is combined with far the greater amount of 
phosphoric acid, the potassium salt normally occurring in only very 
small amounts. 

In addition to the mineral phosphates, phosphoric acid is also 
excreted in combination with glycerine as glycerine-phosphoric acid, 
which need not, however, be considered in a quantitative estimation, 
being present only in traces. 

As in the case of the chlorides, the phosphates are derived from 
two sources, by far the greater part being derived from the food, 
while only a small portion is referable to the phosphorus built up 
in the proteid molecule, be this in the form of a muscle-cell, nerve- 
cell, red blood-corpuscle, or bone. But just as the percentage of 
sulphur varies in the different tissues, so also does that of phos- 
phorus %ary; nerve-tissue, for example, which is very rich in lecithin 
and nucleiu, yields relatively more phosphorus than muscle-tissue. 

Not all the phosphoric acid ingested, however, is excreted in the 



THE URINE. 271 

urine, one-third to one-fourth of the total quantity being eliminated 

in the feces. 

The quantity of P 2 O s excreted, which normally varies between 2.5 
and 3 grammes, is thus largely dependent upon the amount ingested, 
increasing with an animal and decreasing with a vegetable diet. 
During starvation the excretion of P 2 5 is largely increased, in 
consequence, no doubt, of an increased destruction of bone, which 
is very rich in the phosphates of the alkaline earths. In accord- 
ance with this view, calcium and magnesium are excreted in increased 
amount during starvation. The relation between the excretion of 
P 2 O s and N, normally 1 : 7, changes, moreover, in such a manner 
that both the absolute and relative amount of phosphoric acid as 
compared with the nitrogen increases, leading to the conclusion that 
in addition to the muscles some other tissue, rich in phosphorus and 
relatively poor in N, must suffer during the process, the only one that 
suggests itself being bone. 

If at this time food containing phosphorus be again given, a 
retention will take place in the body, so that the general rule 
given in the chapter on Chlorides, that increased elimination is fol- 
lowed by a certain degree of retention, and that a previous retention 
is followed by an increased elimination, seems to hold good for all 
the mineral acids found in the urine (see also the chapter on Sul- 
phates). An increased elimination is also caused by the ingestion of 
large quantities of water, which is followed by a certain degree of 
retention. 

Observations made upon the phosphatic excretion during mus- 
cular exercise have not given uniform results, apparently depend- 
ing upon the nature of the food, as a decrease, no effect at all, and 
an increase have been reported by different observers. Mental exer- 
cise appears to cause a diminished excretion of the alkaline phosphates 
and an increased elimination of the earthy phosphates. The latter 
also takes place during sleep. 

The factors which influence the exact nature of the individual 
phosphatic salts have been considered in the chapter on Reaction, 
in which this has been shown to depend upon the alkalinity of the 
blood, and ultimately upon the quantity of acid set free by the 
tissues or which has been absorbed during the process of digestion • 
increased tissue-destruction, of course, likewise causes an increased 
phosphatic elimination. 



972 CLINICAL DIAGNOSIS. 

Pathologically the total amount of phosphates eliminated in twenty- 
four hours may either be increased or diminished. 

A diminished elimination is observed in most cases of acute febrile 
diseases, such as pneumonia, typhoid fever, typhus fever, recurrens, 
during a paroxysm of intermittent fever, etc., the degree of diminu- 
tion being usually proportionate to the severity of the disease, reach- 
ing its lowest figure as death approaches. Such a state of affairs 
may, at first sight, appear paradoxical, in view of what has been 
said above of the effects of tissue-destruction upon the elimination 
of phosphates. It is necessary, however, to distinguish sharply 
between an increased production and an increased elimination, a 
retention of the phosphates actually set free from the tissues, anal- 
ogous to the retention of chlorides before noted, in all probability 
taking place. It has been supposed that the phosphates set free 
during the process of tissue-destruction are utilized in the building 
up of new leucocytes, an increase in which is actually noted in some 
of the diseases mentioned. 

A diminished excretion of phosphates is, however, not always 
observed, and an increased elimination, on the other hand, may occur 
in certain cases. In fatal cases this condition may even persist 
until the time of death. It is very difficult to give a satisfactory 
explanation of this fact at the present time. The phenomenon, in 
typhoid fever at least, appears to be connected with the intensity of 
the nervous manifestations, and Robin concludes that here an increased 
elimination during the fastigium is an unfavorable omen, while an 
increase during the period of defervescence warrants a favorable 
prognosis. A similar decrease in the phosphates has also been 
observed in pulmonary phthisis associated wuth high fever. 

Very interesting and important is the diminished excretion of phos- 
phates associated with acute and, to some extent also, with chronic 
nephritis, amyloid degeneration of the kidneys, and the anaemias, in 
which an actual insufficiency on the part of the kidneys in the elim- 
ination of these salts appears to exist. 

A diminished, or, at least, no increased excretion is seen in certain 
diseases of the bones, such as osteomalacia, although an increase in 
the earthy phosphates has been noted. This may depend upon either 
a retention or an elimination through other channels. The earthy 
phosphates especially are found in greatly diminished amount, or may 
even be absent altogether in certain cases of nephritis. A similar con- 
dition is observed in acute and chronic rheumatism. 



THE UBINK 273 

During attacks of hysteria major, in contradistinction to epilepsy, 
in which an increased elimination takes place, the phosphates are 
diminished, the degree of diminution being generally proportion- 
ate to the intensity of the attack, increasing again together with 
the other urinary constituents with the subsequent increase in 
the diuresis. The data regarding the phosphatic elimination in 
nervous and mental diseases are, on the whole, very scanty and by 
no means uniform. In chronic lead-poisoning a diminution to one- 
third of the normal quantity may occur. Very low figures have 
been noted in Addison's disease, acute yellow atrophy, in which 
even a total absence may occur, and in certain cases of hepatic 
cirrhosis. 

An increased elimination of phosphates, on the other hand, 
amounting in some cases to 7 or even to 9 grammes for the 
twenty-four hours, has been described under the name of phosjf/iatic 
diabetes, the patient presenting various symptoms commonly seen 
in diabetes mellitus, sugar, however, being usually absent. Whether 
or not phosphatic diabetes is a disease sui generis is not as yet 
certain. 

In true diabetes mellitus a curious relation has been found to exist 
between the elimination of sugar and of phosphates, the quantity of 
the latter rising and falling in an inverse ratio to the amount of 
sugar. In diabetes insipidus a slight increase is at times found.- 

Corresponding to the phosphatic retention observed in acute febrile 
diseases an increased elimination is noted during convalescence. In 
meningitis, especially in cerebro-spinal meningitis, an increase occurs 
in the course of the disease. 

Recently an increase to 7 grammes was noted in a case of pseudo- 
leuksemia, in which the number of red corpuscles fell from 2,200,000 
to 800,000 in four days, and in which, to judge from the very care- 
ful observations made, there could be no doubt that the high degree 
of phosphaturia, which was limited to the alkaline phosphates, was- 
referable to this source. In a case of leukaemia also an increase to 
7 grammes was observed on the day preceding death ; commonly, 
however, the increase is but slight in this disease. 

While it is apparent that important conclusions cannot be drawn, 
on the whole, from a knowledge of the absolute phosphatic elimina- 
tion, unless it be from a study of the relation existing between the 
excretion of the alkaline and earthy phosphates, a study of the rela- 
tive phosphatic excretion seems to promise more valuable results. 

18 



274 CLINICAL DIAGNOSIS. 

According to Ziilzer, a certain amount of the phosphates and of the 
nitrogen is referable to the destruction of albuminous material, 
so that the relation between the phosphoric acid and the nitrogen 
must be a constant one. Another portion, however, is derived 
from lecithin, one of the most important constituents of nerve-tissue, 
containing more phosphorus than the albuminous molecule. When- 
ever, then, the lecithin-containing tissues are more involved in the 
general metabolism than under normal conditions, this relation will 
no longer be a stable one. 

The relation which exists between the elimination of nitrogen and 
phosphoric acid has been termed the Relative Value of phosphoric 
acid. 

The relative value of phosphoric acid in the urine has been calcu- 
lated as varying from 17 to 20, that of the blood being 3, of muscle- 
tissue 12.1, of brain 44, of bone 426 to 430. This value supposes 
the absolute value to vary between 2 and 3 grammes pro die. It is 
found according to the following equation : 



N : P 2 5 : : 100 : x, and x = 1UU ;/ 2^ 5 ? 



100 ^0, 
N 



in which N indicates the amount of nitrogen actually observed, P 2 5 
the amount of phosphoric acid in the same specimen of urine, and 
x the amount of P 2 5 corresponding to 100 grammes of N. By 
observing this relative value a much better idea may be formed of 
the processes taking place in the body in disease than from a mere 
expression of the absolute phosphatic value. 

In acute febrile diseases the relative as well as the absolute diminu- 
tion of the phosphates has been ascribed, as mentioned above, to their 
retention, they being possibly utilized in the building up of white 
blood-corpuscles. In the course of these diseases oscillations in the 
relative value are frequently observed, and an increased relative 
amount would be explained by assuming a transformation of leu- 
cocytes rich in phosphorus into red corpuscles, which are relatively 
poor in phosphorus, resulting in a liberation of P 2 5 . During 
convalescence the relative as well as the absolute value again 
rises. 

In accordance with these considerations a diminished relative ex- 
cretion of phosphoric acid should be expected in all cases associated 
with a notable elimination of pus-corpuscles through other channels, 
as in pneumonia, for example, or a storing away of the same, as 



THE URINE. 275 

in cases of empyema. The i'acts observed are in accord with this 
view. 

A relative decrease has further been noted in the various forms of 
anreniia, conditions of cerebral excitation, and especially preceding 
an attack of epilepsy. In progressive paralysis following syphilis 
the relative value, at first low, rises greatly after the administration 
of potassium iodide, while the excretion of the earthy phosphates is 
lessened. In chronic cerebral affections, delirium tremens, and acute 
hydrocephalus a relative decrease has been noted. In mania, during 
the period of excitement, both the alkaline and earthy phosphates 
are found increased, while during the stage of depression, as also in 
melancholia, the alkaline phosphates are found in diminished and 
the earthy in increased amount. On the other hand, an increase 
in the relative value has been noted in apoplexy (amounting to 
34.3 in one case two days after au attack), brain-tumors, tabes, 
arthritis deformans (30), pernicious anaemia (23.8-58), etc. 

Of drugs potassium bromide appears to diminish the absolute 
amount of phosphoric acid. Cocaine and quinine cause a decrease, 
and salicylic acid an increase. A relative decrease is produced by 
the cerebral excitants, such as strychnine, small doses of alcohol, phos- 
phorus, valerian, cold baths, salt-water baths, etc. An opposite 
effect is produced by the cerebral depressauts, such as chloroform, 
morphine, chloral, large doses of alcohol, potassium bromide, mineral 
and vegetable acids, prolonged cold baths, Turkish baths, low tem- 
perature. 

As is apparent from the data given, our knowledge concerning the 
excretion of phosphoric acid is as yet in its infancy, and the causes 
producing variations in its amount very obscure. It is quite appar- 
ent, nevertheless, that a detailed study, especially of the relative 
excretion of phosphoric acid, would, in all probability, lead to 
highly important results, permitting an insight into the metabolism 
of the individual body-tissues, as it were. In this connection the 
observations of Edlefsen, on the relation existing between the de- 
struction of leucocytes and the excretion of P 2 O s , deserve especial 
mention. 

Practical data as to diagnosis and treatment can, however, not yet 
be formulated. 

Tests for the Phosphates in the Urine. The test for the de- 
tection of the phosphates occurring in the urine depends upon the 
precipitation of phosphoric acid by means of ferric chloride as ferric 



276 CLINICAL DIAGNOSIS. 

phosphate, which is insoluble in cold acetic acid, according to the 

equation : 

2NaH 2 P0 4 -f Fe 2 Cl 6 = Fe 2 (P0 4 ) 2 + 2NaCl + 4HC1, 
or 

2Na 2 HPO« + Fe 2 Cl 6 = Fe 2 (P0 4 ) 2 + 4NaCl +2HC1. 

The same result may be accomplished by the addition of a solution 
of uranyl nitrate, giving rise to the formation of uranyl phosphate, 
which is also insoluble in acetic acid, according to the equation : 

Na 2 HP0 4 4- 2UO.X0 3 =2NaN0 3 + (UO) 2 HP0 4 , 
or 

NaH 2 P0 4 + UO.NO s = NaNO a + UO.H 2 P0 4 . 

Test : A few c.c. of urine are acidified with a few drops of acetic 
acid, and treated with a few drops of a solution of ferric chloride 
(one part of the officinal solution to ten parts of water), when the 
occurrence of a yellowish-white precipitate will indicate the presence 
of phosphates. 

If a solution coutaining an acid phosphate of the alkalies be 
treated with an alkaline hydrate, the diacid alkaline phosphate is 
transformed into the monacid salt, according to the equation : 

NaH 2 P0 4 + ]S T H 4 OH = NaNH 4 HP0 4 + H 2 0. 

This is further changed into the normal salt, as represented in the 
equation : 

3NaNH 4 HP0 4 4- NH 4 OH = Na 3 P0 4 + (NH 4 ) 3 (P0 4 ) 2 4- H 2 0. 

As the monacid and neutral salts are both readily soluble, the 
solution remains clear. If at the same time, as in the urine, a solu- 
ble diacid phosphate of the alkaline earths be present, this is likewise 
transformed into the monacid, and finally into the neutral salt ; the 
latter, however, being insoluble is thrown down : 

I. Ca(H 2 P0 4 ) 2 -4- 4XH 4 OH = Ca(NHJ 2 (P0 4 ) 2 + 4H 2 0. 
II. 3Ca(NH 4 ) 2 (P0 4 ) 2 = Ca 3 (POJ 2 + 2(NH 4 ) 3 P0 4 . 

Test for the earthy phosphates : About 10 c.c. of urine are ren- 
dered alkaline with ammonia, when the occurrence of a flocculent 
precipitate will indicate their presence. 

Test for the alkaline phosphates : After having removed the earthy 
phosphates from 10 c.c. of urine, as just described, the clear filtrate 
is acidified with acetic acid and tested with ferric chloride, or uranyl 
nitrate, as shown above. 

The alkaline phosphates may also be detected by treating the ammu- 



THE URINE. 277 

niacal filtrate with a few drops of magnesia mixture (1 part of crys- 
tallized magnesium sulphate, 2 parts of ammonium chloride, 4 parts 
of ammonium hydrate, and 8 parts of distilled water), when ammo- 
nio-maguesium phosphate, which is almost insoluble in ammonium 
hydrate, will be thrown down, the reaction taking place between the 
monacid or neutral sodium phosphate and the magnesium sulphate, 
according to the equation : 

Xa,HPO,+MgS0 4 +NH 4 OH+NH 4 Cl=MgNH 4 P0 4 +NH 4 Cl+Na,S0 4 +H,0. 

Quantitative Estimation of the Total Amount of Phosphates. 
Principle : When a solution of disodium phosphate, acidified with 
aeetic acid, is treated with a solution of uranyl nitrate, or uranyl 
acetate, a dirty-looking, white precipitate of uranyl phosphate is 
thrown down, which is formed according to the equation given above. 

It is apparent that the quantity of P 2 5 can be estimated accu- 
rately, if the solution of uranyl nitrate or acetate be of known 
strength. 

Solutions required : 

1. A solution of uranium nitrate of such strength that 20 c.c. shall 
correspond to 0.1 gramme of P 2 O s . 

2. A solution containing acetate of sodium and acetic acid. 

3. Tincture of cochineal. 
Preparation of these solutions : 
1. From the equation : 

2UO.N0 3 + Na 2 HPO, = (UO) 2 HP0 4 + 2NaN0 3 

it is apparent that 2 molecules of uranium nitrate combine with 1 
molecule of disodium phosphate to form uranium phosphate and 
sodium nitrate. The molecular weight of uranium nitrate being 318 
and that of disodium phosphate 142, it is seen that 636 parts by 
weight of the former combine with 142 parts by weight of the latter. 

As 20 c.c. of the solution of uranium nitrate correspond to 0.1 
gramme of P 2 5 , 1000 c.c. must be equivalent to 5 grammes of 
P 2 5 . In 142 parts by weight of disodium phosphate there would 
be present 71 grammes of P 2 5 , equivalent to 636 parts by weight 
of uranium nitrate. The quantity of the latter, then, to be dissolved 
in 1000 c.c. of water would be found from the equation : 636 : 71 : : 
x : 5 ; and x = 44.78. 

44.78 grammes of uranium nitrate are weighed off and dissolved 
in about 900 c.c. of water, the solution being purposely made 



278 CLINICAL DIAGNOSIS. 

too strong for reasons pointed out in the chapter on Chlorides. 
In order to bring this solution to its proper strength it is neces- 
sary to titrate with the uranium solution a solution of disodimn 
phosphate of such strength that every 50 c.c. shall contain 0.1 
gramme of P 2 5 , or 1000 c.c. 5 grammes. The molecular weight 
of ]S T a 2 HP0 4 + 12H 2 being 358, this amount of disodium 
phosphate in grammes is equivalent to 179 grammes of P 2 5 ; the 
quantity of P 2 5 corresponding to 5 grammes, in terms of Na 2 HP0 4 — 
12H 2 0, is found from the equation : 358 : 179 : : x : 5 ; and x = 10. 
Ten grammes of pure dry and non-deliquescent Na 2 HP0 4 are dis- 
solved in 1000 c.c. of distilled water. If non-deliquescent diso- 
dium phosphate be not at hand, about 12 grammes of the salt are 
dissolved in 1000 c.c. of distilled water : of this solution 50 c.c. are 
evaporated iu a weighed platinum dish, and the residue gently heated, 
the disodium phosphate being thereby transformed into sodium pyro- 
phosphate, Na 4 P 2 7 , according to the equation : 

2Na,HP0 4 = Na 4 P 2 0, - HX>. 

The molecular weight of Na 4 P 2 0- being 266, this corresponds to 
142 grammes of P 2 5 . 

If the solution were of the correct strength — i.e., containing 0.1 
gramme of P 2 5 iu 50 c.c. of water — the residue should weigh 0.1873 
gramme, as is seen from the equation : 142 : 266 : : 0.1 : x : and x = 
0. 1873. Supposing, however, the residue to weigh 0.1921 gramme, 
it is manifest that the solution is too strong, and must be diluted, 
the degree of the dilution being determined according to the equa- 
tion : 0.1873 : 1000 : : 0.1921 Tx ; and x = 1025: i. e. } 1000 c.c. of 
the solution made must be diluted to 1025 c.c. to make the solution 
of the proper strength. 

In the case given 50 c.c. were used ; the 950 c.c. are then diluted 
with the amount of water found from the equation : 1000 : 1025 : : 
950 : x ; and x = 953.75. Having thus obtained a solution of diso- 
dium phosphate of such strength that every 50 c.c. shall contain 0.1 
gramme of P 2 5 , this solution is titrated with the uranium solution 
which has been made too strong, in order to determine the amount 
of water that must be added to the latter. To this end a Mohr's 
burette is filled with the uranium solution ; 50 c.c. of the disodium 
phosphate solution are treated with a few drops of the tincture of 
cochineal and 5 c.c. of the acetic-acid mixture (see below). This mix- 
ture is heated in a beaker and, as soon as the boiling-point has been 



THE URINE. 279 

reached, titrated with the uranium solution until a trace of a ereenisb 
color is noticed in the precipitate which does not disappear on stirring. 
This point having been accurately determined by means of a second 
titration, the number of c.c. of distilled water with which the re- 
maining solution must be diluted is determined according to the 

N d 
formula : C=^-, in which C represents the number of c.c. which 
n 

must be added, N the number of c.c. remaining after the test-titra- 

tions, u the number of c.c. consumed in one titration to bring about 

the end-reaction, and d the difference between the number of c.c. 

used in one titration and that theoretically required. The amount 

of distilled water necessary for dilution is now added and the solution 

again tested, when 20 c.c. will correspond to 0. 1 gramme of P 2 5 . 

2. The acetic-acid mixture consists of about 100 grammes of ace- 
tate of sodium dissolved in distilled water, and 100 c.c. of a 30 per 
cent, solution of acetic acid, the whole being diluted to 1000 c.c. 

3. Tincture of cochineal. This may be prepared as follows : A 
few grammes of cochineal granules are digested with 250 c.c. of a 
mixture of 3 volumes of water and 1 volume of 94 per cent, alcohol 
in the cold. The solution is theu decanted and ready for use. The 
residue may be utilized in the preparation of a fresh supply of the 
tincture. 

Application to the urine : 50 c.c. of clear, filtered urine are treated 
with 5 c.c of the acetic-acid mixture, the object being to transform 
any monacid sodium phosphate present into diacid sodium phosphate, 
and to neutralize any nitric acid that may be formed during the 
titration, as the nitric acid would otherwise cause a partial solu- 
tion of the precipitated uranyl phosphate. A few drops of the 
tincture of cochineal are added, the mixture heated to the boiling- 
point and titrated as described above, two titrations being usually 
required. 

The results are then calculated as follows : Supposing 15 c.c. of 
the uranium solution to have been used, the corresponding amount of 
P 2 5 contained in 50 c.c. of urine is found from the equation : 
20 : 0.1 : : 15 : x ; and x = 0.075. The percentage-amount would, 
hence, be 0.075 X 2 = 0.15. Supposing the total amount of urine 
to have been 2000 c.c, the elimination of P 2 5 would correspond to 
3 grammes. 

The presence of sugar and albumin does not interfere with this 
method. 



280 CLINICAL DIAGNOSIS. 

Separate Estimation of the Earthy and Alkaline Phos- 
phates. If the alkaline and earthy phosphates are to be deter- 
mined separately, the total amount of P 2 O s is estimated in one portion 
of the urine, while the P 2 5 in combination with the alkaline earths 
is determined in another, as follows : 

Two hundred c.c. of filtered urine are made strongly alkaline 
with ammonium hydrate and set aside, covered, for several hours, 
when the earthy phosphates thus precipitated are collected upon a 
filter, -washed with dilute ammonia (1 : 3), and then transferred to a 
beaker with the aid of a little water, containing a few drops of acetic 
acid, by perforating the filter. They are then dissolved with as little 
acetic acid as possible, diluted to 50 c.c. with distilled water, and 
titrated with the uranium solution as described. The difference 
between the total amount of P 2 0. and the amount thus obtained is 
the quantity of alkaline phosphates present. 

Removal of the Phosphates from the Urine. Whenever it 
is necessary to remove the phosphates from the urine in the course 
of an analysis, as is frequently the case, the urine is rendered alkaline 
by the addition of the hydrate of an alkaline earth and precipitated 
with a soluble calcium or barium salt. The phosphates may also be 
precipitated by means of neutral or basic acetate of lead, in which 
case the excess of lead is removed by means of sulphurated hydrogen 
or dilute sulphuric acid. 

The Sulphates. 

The sulphuric acid found in the urine is derived essentially from 
the albuminous material which is constantly broken down in the 
body, only a very small portion of the inorganic sulphates excreted 
being referable to the mineral constituents of the food. As was 
pointed out in the chapter on Reaction, sulphuric acid is constantly 
being produced in the body, and, coming into contact with the so-called 
neutral phosphates present in almost all the tissues, transforms these 
into acid phosphates taking up the alkali thus set free, according to 
the equation : 

2Na 2 HP0 4 -f H 2 SO, = 2NaH 2 PO -f Xa 2 S0 4 , 

both appearing in the urine. The alkaline carbonates, derived from 
the organic salts ingested by a process of oxidation, are also attacked 
by the sulphuric acid. 

As the amount of food ingested is gradually diminished a point is 
reached when the body most tenaciously holds any alkaline salts 



THE URINE. 281 

that may still be present, and a new source lor the neutralization oi 
the acid is found in the ammonia, which would otherwise have been 
transformed into urea. 

While the greater portion of the sulphuric acid excreted in the 
urine is found in the form of mineral sulphates, about one-tenth of 
the total amount may be shown to be in combination with aromatic 
substances belonging to the oxy-group, most important among these 
being the salts of phenol, indoxyl, and skatoxyl. 

Indoxyl and skatoxyl, as will be shown later on, are derived from 
indol and skatol, which, together with phenol, are formed during the 
process of intestinal putrefaction, their amount increasing and de- 
creasing with the degree of putrefaction, and hence serving as a direct 
index of its intensity. 

The mineral sulphates have been termed preformed sulphates, in 
contradistinction to the others w T hich are known as conjugate or ethe- 
real sulphates. In the following pages the former will be designated 
by the letter A, the conjugate sulphates by the letter B, and the total 
sulphates as A + B. 

The amount of A -j- B excreted in the twenty-four hours by a nor- 
mal individual varies between 2 and 3 grammes, the ratio of A to 
B being as 10 : 1. 

From what has been said it is apparent that the elimination of 
sulphates through the urine is largely dependent upon the degree of 
albuminous decomposition taking place in the tissues and fluids of 
the body, and hence to a certain extent upon the quantity of proteid 
material ingested, the mineral sulphates occurring in such small 
amount in the food as scarcely to affect the quantity excreted. Sec- 
ondarily, the degree of intestinal putrefaction plays a role. The 
excretion of A -^ B is thus increased by a diet rich in animal pro- 
teids ; the time after a meal at which such an increase can be demon- 
strated varies greatly, depending essentially upon the time necessary 
for digestion. With a vegetable diet, on the other hand, the total 
sulphates will be found in diminished amount. During starvation, 
A -j- B is, of course, also diminished, this diminution affecting A 
especially, but in some cases B also is considerably increased. 

Our present knowledge regarding the excretion of sulphates is 
very meagre, as may be seen from the following data : An increase 
in the elimination of the total sulphates is observed, as would be 
anticipated, in all cases in which an increased tissue-destruction is 
taking place, as in the acute febrile diseases. It must be remem- 



282 CLINICAL DIAGNOSIS. 

bered, however, that here the quantity excreted is not always greater 
than during convalescence, the diet remaining the same. Here, as 
elsewhere, in urinary studies, it is always necessary to distinguish 
between a relative increase and an absolute decrease. In pneumonia 
and acute myelitis the highest figures have been observed, the in- 
creased elimination during the febrile period being especially marked : 

Fever diet. Full diet. 





Fever. 


No fever. 


No fever. 


Pneumonia 


. 3.51 g. 


1.47 g. 


2 25g. 


Acute myelitis . 


. . 2.62 g. 


1.52 g. 


2.33 g. 



During convalescence the excretion of the sulphates is diminished, 
a retention analogous to that of the chlorides and phosphates taking 
place. In contradistinction to the latter salts, it is in all probability 
not the mineral matter proper that is demanded by the body, but the 
sulphur- containing albuminous material. 

A considerable elimination of A -f- B has also been observed in 
cases of leuksemia in which an average of 2.46 grammes is excreted, 
as compared with 1.51 grammes by a healthy individual receiving the 
same amouut and kind of food. In one case of acute leukaemia 5.8 
grammes were eliminated on the day preceding death. In diabetes 
mellitus, diabetes insipidus, oesophageal carcinoma, progressive mus- 
cular atrophy, pseudo-hypertrophic paralysis, and eczema an increased 
elimination has likewise been observed, while in chronic renal diseases 
a diminished excretion is the rule. 

A study of the elimination of the conjugate sulphates and of the 
relation existing between A and B in disease is still more important 
than that of the total sulphates, but in both cases the data available 
at the present time are very scanty, and further observations are 
urgently needed. 

The conjugate sulphates, as would be expected, are increased in all 
cases of increased intestinal putrefaction. In coprostasis the result 
of carcinoma the ratio of the preformed to the conjugate sulphates, 
normally 10, may diminish enormously. In one case, reported by 
Kast and Baas, it fell to 2, to rise again to 7 to 8, and finally to 
9.5 to 15 after an artificial anus had been established. The author 
has observed a drop to 1.5 in a case of volvulus of ten days' stand- 
ing. Biernacki found an increase in the elimination of conjugate sul- 
phates amounting to from 0.15 to 0.5 gramme pro die in cases of 
chronic parenchymatous nephritis, going hand in hand apparently 
with a decrease in the secretion of hydrochloric acid by the stomach, 



THE URINE. -js:; 

the normal amount, according to his observations, being from 0.1973 
to 0.2227 gramme. In one case B fell from 0.4382 to ( ). 1 5< ><") during 

the administration of hydrochloric acid, to increase again to 0.4127 
upon its discontinuance. 

In accord with these observations are those of Wasbutzki and Kast, 
the former finding an increased elimination of B in cases of intense 
bacterial fei mentation taking place in the stomach, hydrochloric acid 
being either totally absent or present in greatly diminished amount, 
while a diminished elimination was observed in cases of intense toru- 
lar fermentation, hyperchlorhydry existing at the same time. In the 
absence of hydrochloric acid, a normal or even a slightly diminished 
amount was observed in cases of intense acid fermentation, lactic and 
butyric acids being present in large quantities. 

By neutralizing the gastric juice with large doses of sodium bicar- 
bonate Kast was able to bring about a marked increase in the 
elimination of B, the ratio A : B having fallen from 10.3-16.1 to 
2.9-6.1. 

Personal observations have led the author to the same conclusion, 
so that the following rules may be formulated : 

1. A diminution in the secretion of hydrochloric acid is accompa- 
nied by an increased degree of intestinal putrefaction. 

2. An increase in the secretion of hydrochloric acid is accompauied 
by a decrease in the degree of intestinal putrefaction. 

3. The degree of intestinal putrefaction may be measured directly 
by the elimination of the conjugate sulphates. 

(See also the chapter on the Aromatic Bodies.) 

In obstructive jaundice the excretion of B w r as likewise found to 
be increased, returning to the normal as soon as the permeability of 
the biliary passages had again become established, while the total 
sulphates were found in diminished amount in cases of non-obstruc- 
tive jaundice. 

In cases of diarrhoea A -f- B, as well as B, is diminished, while 
A : B is increased. 

Of drugs, large doses of morphine, potassium bromide, sodium 
salicylate, and antifebrin appear to cause an increased elimination of 
the total sulphates, while alcohol slightly diminishes the excretion. 

Most important are the observations which have established a 
diminished excretion of the conjugate sulphates following the inges- 
tion of the terpenes and camphor, Karlsbad and Marienbad water, 
which latter two, however, at first cause an increase. Kefir, in doses 



284 CLINICAL DIAGNOSIS. 

of from 1 to 1.5 liters pro die, has proved a most excellent remedy 
with which to check intestinal putrefaction. Injections of tannic 
acid and of a saturated solution of boric acid appear to produce 
but little effect, unless the dose be so large as to cause symptoms of 
poisoning. 

The points of practical interest in connection with the elimination 
of the sulphates may be summarized as follows, and are concentrated 
in the elimination of the conjugate sulphates : 

1. An increase in the conjugate sulphates in a general way points 
to increased intestinal putrefaction, the direct cause for which must, 
according to our present knowledge, be sought in a total anachlor- 
hydry, or at least a hypochlorhydry of the gastric juice, associated 
with intense bacterial fermentation, provided that lactic acid and 
butyric acid are not present in large amounts ; an obstruction to the 
flow of bile and intestinal obstruction may, however, produce the 
same result. 

2. A diminution in the quantity of conjugate sulphates, on the 
other hand, may be referable to hyperchlorhydry associated with 
torular fermentation, ulcer of the stomach forming an exception, in 
which, notwithstanding the fact that conjugate sulphates are frequently 
eliminated in increased amount, hyperchlorhydry usually exists. 

3. In cases of diarrhoea the absolute as well as the relative 
quantity of A -f- B and B is diminished while A : B becomes 
greater. 

Tests for the Sulphates in the Urine. The detection of the 
preformed and the combined sulphates in the urine depends upon the 
fact that the sulphates of the alkalies are precipitated by barium 
chloride as insoluble barium sulphate, according to the equation : 

K 2 S0 4 H- BaCl 2 = BaS0 4 + 2KC1. 

In the urine the addition of barium chloride at the same time causes 
a precipitation of the phosphates, which must be kept in solution by 
the addition of an acid, acetic acid being employed for this purpose 
whenever the presence of the preformed sulphates is to be demon- 
strated; hydrochloric acid is inadmissible, as it would cause decom- 
position of the conjugate sulphates and set free the H 2 SO thus held. 
To test for the preformed, sulphates a few c.c. of urine, strongly 
acidified with acetic acid, are treated with a few drops of a solution 
of BaCl 2 , when in their presence a cloud or a white precipitate, refer- 
able to the formation of BaS0 4 , will form. 



THE URINE. 285 

To test for the conjugate sulphates, 25 c.c. of urine arc treated 
with about the same volume of an alkaline barium chloride mix- 
ture (2 volumes of a solution of barium hydrate and 1 volume 
of a solution of barium chloride, both saturated at ordinary temper- 
atures) and filtered after a few minutes, the preformed sulphates as 
well as the phosphates being thus removed. The filtrate is then 
strongly acidified with hydrochloric acid and boiled, when the occur- 
rence of a precipitate will be referable to conjugate sulphates. 

Quantitative Estimation of the Sulphates. The principle 
of the method employed is the same as that just described, the pre- 
formed sulphates contained in the urine forming an insoluble precip- 
itate of BaS0 4 when treated directly with BaCl 2 , while the combined 
sulphates do so only after having been decomposed by the addition 
of strong muriatic acid and the application of heat. In order to 
estimate the amount of preformed and conjugate sulphates in the 
urine it is best to determine the total sulphates in one portion, and 
the combined sulphates in another, the difference between the two 
giving the preformed sulphates. 

Quantitative Estimation of the Total Sulphates. One 
hundred c.c. of clear, filtered urine are treated with 8 c.c. of hydro- 



Fig. 7 




A Gooch filter. 

chloric acid (specific gravity 1.12) and heated to the boiling-point, 
when 20 c.c. of a saturated solution of BaCl 2 are added. The mix- 
ture is kept on the water-bath until the BaS0 4 has thoroughly settled 
down and the supernatant fluid appears clear; this usually requires 
about half an hour. The precipitate is now filtered off, a Schleich 
and Schiill filter, or, still better, a Gooch filter (Fig. 76), provided 
with a close-fitting plug of asbestos, being employed, the whole hav- 
ing been previously dried and weighed. Care should be taken never 



286 



CLINICAL DIAGNOSIS. 



Fig. 77. 



to allow the filter to become dry, and small amounts of hot water 
must be added to the last e.c. remaining, the final traces being placed 
upon the filter with the aid of a rubber-tipped glass rod. The pre- 
cipitate is washed with boiling water until a specimen of the wash- 
ings is no longer rendered cloudy, even on standing for a few minutes, 
on the addition of a drop of dilute sulphuric acid. Gum-like sub- 
stauces, as well as pigments, are removed by washing with hot alcohol 
(70 per cent.), and then filling the filter two or three times with ether. 
A suction-apparatus is necessary, and in the ab- 
sence of a special pump a simple glass tube bent 
upon itself may be employed (Fig. 77). 

If a paper filter has been used, it is placed in a 
weighed platinum or porcelain crucible and ignited. 
The ash is then heated, at first moderately, and 
almost completely covered with the lid. It is then 
heated, only half covered, from five to seven min- 
utes, until the contents of the crucible are white. 
The crucible when cooled is placed in a desiccator 
and weighed, the difference between the first and 
the second weight giving the Aveight of the BaS0 4 
obtained from 100 c.c. of urine. 

A reduction of some of the BaS0 4 usually takes 
place during the process of combustion, owing to 
the presence of organic material, so that the weight 
of the BaS0 4 obtained is actually too low. This 
error may be corrected in the following manner : 
The BaS0 4 is washed into a small beaker with a 
small amount of water, colored red by a few drops 
of an alcoholic solution of phenolphthalein, and 
titrated with a one-tenth normal solution of sul- 
phuric acid until the red color has disappeared. 
Every c.c. of the one-tenth normal solution cor- 
responds to 0.004 gramme of BaS0 4 , so that the 
actual amount of BaS0 4 contained in 100 c.c. of 
urine is ascertained by adding the figure thus found to that obtained 
by weighing (see below). 

Quantitative Estimation of the Conjugate Sulphates. 
One hundred c.c. of clear, filtered urine are mixed with 100 c.c. of 
an alkaline solution of BaCl 2 (see above), the mixture being thor- 
oughly stirred. After a few minutes this is filtered through a dry 




A suction-funnel. 



THE URINE. 287 

filter into a dry graduate up to the 100 e.e. mark. This portion, 
corresponding to 50 e.e. of urine, is now strongly acidified with 
dilute hydrochloric acid and brought to the boiling-point. It is 
kept upon the boiling water- bath until the BaSC) 4 formed has settled 
and the supernatant fluid is clear. The precipitate is filtered off, 
washed, dried, and weighed, as described above. The BaS0 4 thus 
obtained multiplied by 2 and deducted from the amount found accord- 
ing to the first method indicates the amount referable to the preformed 
sulphates. The molecular weight of BaS0 4 being 232.82, that of 
S0 3 79.86, of H 2 S0 4 97.82, and of S 32, the figure expressing the 
amount of H 2 S0 4 , S0 3 , or S, corresponding to 1 gramme of BaS0 4 , 
is found according to the following equations : 

232.82 : 79.86 : :1 :x, and x = 0.34301. .\ 1 gramme of BaSO, 
= 0.34301 gramme of S0 3 . 

232.82 : 97.82 : : 1 : x, and x = 0.42015. . \ 1 gramme of BaS0 4 
= 0.42015 gramme of H 2 S0 4 . 

232.82 : 32 : : 1 : x, and x = 0.13714. .\ 1 gramme of BaS0 4 = 
0.13744 gramme of S. 

To calculate results it is only necessary to multiply the weight of 
BaS0 4 found by 0.34301, 0.42015, or 0.13741 in order to ascertain 
the amount of sulphuric acid contained in 50 c.c. of urine in terms 
of S0 3 , H 2 S0 4 , or S, respectively. 

Urea. 

Urea is by far the most important nitrogenous constituent of the 
urine, representing under normal conditions 85 to 86 per cent, of 
the total amount of nitrogen eliminated by the kidneys. Chemically 
it may be regarded as carbamide — I. e,, as the amide of carbonic 
acid — and represented by the formula : 

NH 2 

co- 

X NH 2 

being thus a comparatively simple substance, and the question natur- 
ally suggests itself, In what relation does urea stand to the highly 
complex albuminous molecule from which it is derived? Numerous 
hypotheses have been offered to explain this most difficult problem, 
and, although we are in possession of a number of very suggestive 
data, an ultimate answer to the question cannot be given at the 
present time. 

AVhen albumin is treated with strong acids or alkalies, leucin, 



288 CLINICAL DIAGNOSIS. 

tyrosin, and asparaginic acid are formed, bodies which belong to the 
group of amido-acids, being represented by the formulae : 

C 5 H 10 (NH 2 ) OH COOH 

I C e H/ C 2 H 3 (NH 2 )^ 

COOH x C 2 H 3 (NH 2 )COOH X COOH 

Leucin. Tyrosin. Asparaginic acid. 

These bodies were regarded by Schultzen and Nencki as intermediate 
products in the formation of urea. As a matter of fact, it was shown 
that leucin, asparaginic acid, and glycocoll, 

CH 2X 

x COOH 

which latter can be obtained under similar conditions from connec- 
tive tissue, osseous and gelatinous tissue, are transformed, to a large 
extent at least, into urea within the body. An analogous formation 
of urea was hence supposed to occur, the transformation of amido- 
acids into uric acid occurring in birds being regarded as supporting 
this view, uric acid in birds corresponding to urea in mammals. 
The manner of the transformation of amido-acids into urea in the 
body is unknown. It is conceivable that hydrocyanic acid (CONH), 
for example, may be produced as an intermediate product, the for- 
mation of urea resulting from an interaction between 2 molecules of 
CONH in statu nascendi, according to the equation : 

/NH 2 
CONH + CONH + H 2 = CO( + C0 2 . 

X NH 2 

A transformation of the amido-acids into the ammonium salts of the 
fatty acids standing next in order in the downward scale may also be 
imagined. This change being produced by a process of oxidation, 
the salts of the fatty acids would then be transformed into ammo- 
nium carbonate and this again into urea. 

In the case of glycocoll such a process would be represented by 
the following equations : 

I. CH 2 .NH 2 .COOH + 20 = H C0 2 .NH 4 + C0 2 . 
Amido-acetic acid. Amnion, formate. 

II. 2H.C0 2 .NH 4 + 20 = (NHJ 2 C0 3 + H 2 + C0 2 . 
Ammon. formate. Ammonium carbonate. 

/NH 2 
III. (NHJ 2 C0 3 = CO( +2H 2 0. 
X NH 2 

The possible formation of urea from ammonium carbonate in the 
body has been demonstrated by v. Schroeder and Salomon, who 



THE URINE. 289 

observed a fair production of urea when blood containing ammo- 
nium carbonate or ammonium formate was allowed to flow through 
isolated livers of dogs. 

Other hypotheses have been offered to explain the mode of forma- 
tion of urea, such as its production from ammonium carbonate, 
formed directly from albuminous material without the intermediate 
occurrence of amido-acids. 

According to Drechsel, the amido-acids are transformed into car- 
bamic acid, 2 molecules of the latter uniting to form urea, carbonic 
acid, and water : 

,XH 2 .NH 2 .NH 2 

CO; + CO ( = CO< + C0 2 -f H 2 0. 

x OH x OH X NH 2 

On the other hand, it does not necessarily follow that urea is 
always formed in the same manner, and the possibility of its for- 
mation from kreatin and xanthin bases cannot be altogether excluded. 
It is at the same time conceivable that urea may under certain con- 
ditions be produced in a different manner by different organs. 

Numerous experiments have been made in order to ascertain defi- 
nitely in what organ or organs urea is formed during health, and 
special attention has been directed to the kidneys, the muscular tissue, 
and the liver. 

Opposed to the assumption that urea is formed in the kidneys 
are the facts that after extirpation of these organs an accumulation 
of urea is observed in the blood and tissues of the body, and that 
experiments analogous to those made with still living livers furnished 
a negative result. 

The same result has been reached as far as the muscular tissue of 
the body is concerned, although the curious fact that more urea is 
found in these organs than in the blood of nephrectomized animals, 
in the typhoid stage of cholera asiatica, etc., has so far not been ex- 
plained. Under normal conditions, however, urea has not been 
demonstrated in the muscles. 

There remained then for consideration the large glandular organs 
of the body, especially the liver and spleen, in which urea is always 
demonstrable. In the former organ the transformation of ammo- 
nium carbonate and the ammonium salts of the fatty acids has been 
conclusively established. The facts that possible antecedents of urea, 
such as leucin, have been observed in the absence of urea in the 
urine, in cases of acute yellow atrophy, and that an increase in the 

19 



290 CLINICAL DIAGNOSIS. 

elimination of ammonia goes hand in hand with a diminished excre- 
tion of urea in certain diseases of the liver, also speak strongly in 
favor of the hepatic origin, to a large extent at least, of urea. 

Before going on to a consideration of the quantitative excretion of 
urea in health and disease, it will be well to form an idea of its ulti- 
mate sources. To this end the theory of Pettenkoffer should be 
recalled, according to which albuminous material exists in the body 
in two different forms; i.e., as organized albumin, which is built up 
in the form of tissues of the body, and as unorganized albumin, or 
circulating albumin, which must be regarded, in a manner, as a 
reserve, to be used in tissue-repair, to be broken down if not used, 
and to be replaced by the proteids ingested with the next meal. It 
may, hence, be said that, as in the case of the mineral constituents 
of the urine, the urea found in the urine is referable on the one hand 
to the proteids of the food, and on the other to the proteids of the 
body-tissues. It is clear then that the elimination of urea will con- 
tinue during deprivation of food. 

It has been stated that 84 to 86.6 per cent, of all the nitrogen 
eliminated in the urine is found in the form of urea, the remaining 
13.4 per cent, being excreted as uric acid, hippuric acid, kreatinin, 
xanthin bases, etc. It might, hence, be supposed that an accurate 
idea of the degree of tissue-destruction could be formed from a quan- 
titative estimation of urea. This, however, is not the case, espe- 
cially in pathologic conditions, as the quantitative relation existing 
between the excretion of urea and the remaining uitrogenous con- 
stituents is subject to wide variations. In acute yellow atrophy, 
for example, as pointed out above, urea may disappear entirely from 
the urine, the nitrogen being eliminated in the form of other com- 
pounds. Whenever it becomes desirable then to gain an accurate 
insight into the degree of proteid-destruction or proteid-assimilation 
— in other words, into the nitrogenous metabolism — taking place in 
the body, it is necessary to resort to a quantitative determination of 
the total amount of nitrogen excreted by the kidneys, the quantity 
found being conveniently expressed in terms of urea. At the same 
time it is customary to express the amount of proteid tissue de- 
stroyed as muscle-tissue, this serving as a fair type of body-tissue 
in general. 

As 100 grammes of lean muscle-tissue contain about 3.4 grammes 
of nitrogen, corresponding to 7.286 grammes of urea, 1 gramme of 
the latter is equivalent to 13.72 grammes of muscle- tissue. It is, 



THE I'll I Si:. 091 

hence, only necessaiw to multiply the quantity of urea eliminated in 
the twenty-four hours, corresponding to the total amount of nitrogen 
found, by 13.72, in order to form an idea of the extent of albuminous 
destruction taking place in the body. If accurate results are to be 
obtained, it also becomes necessary to determine the amount of nitro- 
gen eliminated in the feces, a knowledge of the quantity in the food 
ingested being, of course, presupposed. 

With all these data given the nitrogenous metabolism of the body 
can be accurately controlled. 

Example : A patient eliminated 50 grammes of urea in twenty- 
four hours ; these 50 grammes correspond to 50 X 13.72 — i.e., QS6 
grammes of lean muscle-tissue ; he ingested, on the other hand, an 
amount of nitrogenous material corresponding to only 10 grammes 
of urea, equivalent to 10 X 13.72 — i.e., 137.2 grammes of muscle- 
tissue. The difference between the amount ingested and that excreted 
in this case — i. e., 548.8 grammes — must be referable to the destruc- 
tion of organized albumin. 

The valuable results of such a study in different cases, and the 
insight that can thus, and only thus, be obtained into the metabolic 
processes taking place in the body, are apparent, but such studies 
are, unfortunately, greatly neglected. 

When the amount of nitrogen eliminated is equivalent to that 
ingested nitrogenous equilibrium is said to exist. A healthy person 
may be said to be approximately in this condition. 

It has been pointed out that during starvation urea is still elimi- 
nated from the body, although in diminished amount. The question 
now arises, What happens if at this time an amount of nitrogenous 
food is given which corresponds exactly in amount to that elimi- 
nated ? Under such conditions an increased elimination of nitrogen 
takes place, all of the nitrogen ingested, in addition to that resulting 
from a breaking down of tissue, being excreted. The amount of 
nitrogen referable to the latter source, however, is somewhat less 
than that eliminated in the total absence of food. Unless starvation 
has been pushed too far, the body accommodates itself to the amount 
of food thus given and nitrogenous equilibrium is restored. If more 
food be allowed, an increased elimination results, again leading to a 
condition of nitrogenous equilibrium, different levels, so to speak, 
being possible. This is well illustrated by comparing the condition 
of the poorly nourished North German laboring population with that 
of the. well-fed merchants, the excretion of urea iu the former amount- 



_■.-_ jumcAi dla -y : ; : ; . 

ing only to 17.5 to 33.5 grammes of area, and in the latter to 30 

It is apparent, then, that the elimination of area, and of nitro- 
gen in general, is subject to great variations, depending upon the 
amount ingested and that resulting from tissue-destruction, which 
in turn is largely influenced by the body-weighr. A statement in 
figures, expressing the daily elimination of urea and of nitrogen 
would, hence, be of very little value, especially in pathologic condi- 
tions, in which the amount of nitrogen ingested is frequently v 
small On the whole, it may be said that the elimination of nitro- 
gen should always be compared with the amount ingested, for which 
purpose the tables of Konig will be found most convenient. At the 
same time, it must be remembered that not all the nitrogen taken 
into the body as food undergoes resorption, and that a variable 
amount, which in disease may be considerable, is eliminated with the 
feces, so that in accurate work this nitrogen must be taken into ac- 
count. In order to obviate the tedious estimation of nitrogen in the 
feces, it has been proposed to determine the standard amount of urea 
which should appear in the urine of a healthy person with different 
forms of diet. Such experiments, of course, presuppose the control- 
person to be in a condition of nitrogenous equilibrium, which, from 
what has been said above, is readily accomplished, the hnman 1 
adapting itself with ease to different forms of diet. In private practice, 
however, such a procedure would be difficult, and here approximate 
results can be obtained by a parallel estimation of the chlorides. In 
health the elimination of the chlorides may be placed at about one- 
half of the urea. Whenever the nitrogen res __ from tissue- 
destruction is in excess of that referable to the proteids ingested this 
relation between the excretion of chlorides and urea will be disturbed, 
the tissues of the body containing but very little sodium chlori 
Whenever the amount of urea is in excess of the normal amount of 
chlorides, as indicated above, an increased tissue-destruction may be 
inferred, and rice versa. If, on the other hand, the chlorides are 
present in diminished amount, the conclusion may he drawn that a 
retention of albumins is taking place in the body, a condition which 
is frequently observed during the convalescence from acnte febrile 



increase in the amc li ~ ureOj and, as a matter of fact, of all 
the nitrogenous constituents, is observed especially in the acute : 
diseases, notwithstanding the diminished ingestion of nitrogenous 



THE URINK 293 

material, and is due to the greatly increased tissue- destruction. 
An excretion of 50 grammes or more of una is here frequently ob- 
served. Formerly it was thought that the fever itself w as responsible 
for this increased elimination of urea; but this view became untenable 
wheu it was shown that the excretiou of urea in the beginning of a 
febrile attack is not at all proportionate to the height of the tempera- 
ture, reaching its highest point only when the fever has been coutinnous 
for several days. Still larger amounts, moreover, may be eliminated 
when the fever is abating. Similar observations have since been 
repeatedly made. An increased elimination of nitrogen may be 
noted in almost every case of ague preceding the onset of the fever. 
The latter, therefore, cannot be the only factor which causes the in- 
creased excretion of urea, and it has been suggested that the cells of 
the body have lost the power of taking up nitrogen. The question, 
however, whether this is dependent upon the increase in temperature 
or the action of certain toxic substances circulating in the blood, or 
both, must still be regarded as unanswered. 

The large increase in the elimination of nitrogen in febrile diseases 
is especially striking in those forms which end by crisis. This is 
notably the case in pneumonia,in which it may persist for two or three 
days after the occurrence of the crisis. The assumption of an under- 
lying insufficiency on the part of the cells furnishes a very satisfac- 
tory explanation for the continued increased elimination of urea, an 
increase beyond the amount eliminated during the febrile stage being 
possibly owing to a certain degree of retention which has been seen 
to occur in the case of the mineral constituents of the urine. 

The only exception to the rule that the excretion of urea is in- 
creased in acute febrile diseases is, apparently, acute yellow atrophy, 
in which the excretion of urea is not only greatly diminished, but 
may altogether cease, its place being taken by other nitrogenous 
bodies, and notably leuein and tyrosin. 

Among afebrile diseases in which an increased elimination of urea 
has been noted must be mentioned the ordinary forms of dia- 
betes mellitus, in which the highest figures have been obtained, viz , 
150 grammes or more pro die. The observation is, in all proba- 
bility, largely explained by the ingestion of excessive amounts 
of food by such patients, but carefully conducted experiments seem 
to show that a not inconsiderable portion of the urea is directly due 
to increased tissue-destruction. The interesting cases described by 



294 CLINICAL DIAGNOSIS. 

Hirschfeld, which will be considered later on, form an exception to 
this rule. 

An increase is also observed in dyspnoeic conditions, aDd particu- 
larly iu pneumonia, being most marked on the day following the 
greatest difficulty in breathing. These observations, however, are 
not free from objections, as an increase has also been noted in con- 
ditions of apnoea. 

A moderate increase has been found in cases of pernicious anaemia, 
in severe cases of leukaemia, scurvy, minor chorea, and paralysis agi- 
tans. Observations made in cases of hystero-epilepsy have given 
rise to conflicting results. It is claimed, on the one hand, that the 
excretion of urea is diminished following the convulsive seizures of 
a hystero-epileptic nature, in contradistinction to an increased elim- 
ination following true epileptic attacks. 

In cases of functional albuminuria associated with an increased 
elimination of uric acid or oxalic acid, or of both, as well as in num- 
erous cases of gastro-intestinal disease, the author has observed an 
increased elimination of urea, and believes that in the treatment of 
these diseases a systematic study of the excretion of nitrogen is of 
fundamental importance. 

Of drugs, an increased elimination is produced by coffee, caffein, 
morphine, codeia, ammonium chloride, sodium and potassium chlo- 
ride, carbonate of lithia, the ingestion of large amounts of water, etc. 
The data concerning the action of quinine, salicylic acid, cold baths, 
etc., are very conflicting. A large increase has been observed in 
cases of phosphorus-poisoning. 

Electricity also appears to exert a distinct influence upon the ex- 
cretion of urea, producing an increased elimination. 

The diminished elimination of urea observed in certain diseases 
of the liver, notably in acute yellow atrophy, carcinoma, cirrhosis, 
and even in Weyl's disease, is of especial interest, being in perfect 
accord with the theory that the liver is the main seat of the produc- 
tion of urea. 

As has been stated, urea may altogether disappear from the urine 
in acute yellow atrophy and also in WeyFs disease, notwithstanding 
the frequently not inconsiderable degree of fever. In cirrhosis, 
hyperemia of the portal system has been thought to cause the 
diminution, which may be further increased in some cases by the 
occurrence of ascites. In short, the factors which may be regarded as 



THE URINE. 995 

causative iu the production of a diminished elimination of urea in 
hepatic diseases may be summarized under the following headings : 

1. Destruction of the hepatic parenchyma. 

2. A diminished velocity of the flow of blood through the liver, 

3. Insufficient excretion of bile, and coincident digestive disturb- 
ances. 

Whenever there is disease affecting that portion of the renal paren- 
chyma which is especially concerned in the elimination of urea a 
diminished amount will, of course, be met with in the urine, and 
carefully conducted observations upon the excretion of the various 
urinary constituents would undoubtedly be of considerable value 
from a diagnostic as well as a therapeutic standpoint. As the glom- 
eruli of the kidueys are mainly concerned in the elimination of water 
and salts from the blood, aud as the striated epithelium of the convo- 
luted tubules appears to provide for the excretion of urea, the elimi- 
nation of a fair amount of the latter with a diminished elimination 
of salts, the phosphates being here of especial interest, as they are 
derived to a large extent from albuminous material, would point more 
particularly to glomerular disease. On the other hand, a fair excre- 
tion of phosphates and a diminished excretion of urea would be 
indicative of tubular disease. Whenever the glomeruli and tubuli 
coutorti are equally diseased, an insufficient elimination of both 
phosphates and urea will be observed. 

While, as a rule, the excretion of urea is greatly increased in dia- 
betes mellitus, certain cases which have been elaborately described by 
Hirschfeld must be excepted. His researches have established beyond 
a doubt that the resorption of nitrogeuous material from the intestines 
may be very much below normal, and with it the elimination of urea. 
Upon these grounds he has advocated the recognition of a distinct 
form of diabetes, which is characterized by a comparatively rapid 
course, the occurrence of colicky abdominal pains before or at the onset 
of the diabetic symptoms proper, the existence of pancreatic lesions in 
a certain proportion of cases, a more moderate degree of polyuria, etc. 

In mental diseases a diminished excretion of urea has been observed 
in melancholia and iu the more advanced stages of general paresis, 
while an increase is associated with the increased ingestion of food 
during the first stage of profound dementia. 

Followiug epileptic, cataleptic, and hysterical seizures, as well as 
in pseudo-hypertrophic paralysis, a decrease has been noted by some 
observers. 



296 CLINICAL DIAGNOSIS. 

The diminished excretion found in Addison's disease has also been 
regarded as being of nervous origin. 

All forms of chronic, non-progressive anaemia are associated with 
a decrease, as are also osteomalacia, impetigo, lepra, chronic rheuma- 
tism, etc. In chronic lead-poisoning the elimination of urea may be 
greatly diminished. 

Of the influence of drugs in bringing about a diminished excretion 
of urea but little is known. 

In conclusion, the relation existing between phosphatic excretion 
and that of nitrogen should be especially noted, and the reader is 
referred to that chapter. 

Properties of Urea. Urea crystallizes in two forms, viz., in 
long, fine white needles, if rapidly formed, or in long, colorless quad- 
ratic rhombic prisms when allowed to crystallize gradually from its 
solutions. 

At 100° C. it begins to show signs of decomposition, at 130° to 
132° C. it melts, and when heated still further it is decomposed into 
cyanic acid and ammonia, of which the former is immediately trans- 
formed into its polymeric compound, cyanuric acid, the reaction which 
takes place being represented by the equations : 



y 



NH 2 



I. COC = COXH + NH 3 . 

X XH 2 

II. 3COXH = CAN 3 H 3 . 

Biuret is formed as an intermediate product during this decompo- 
sition, 2 molecules of urea yielding 1 molecule of ammonia and 1 
molecule of biuret, as represented in the equation : 

XH 2 /NHj 

CO( CO; 

*g* = NH + >'H, 

co; co; 

X NH 2 ^NH 

As this substance, which may be obtained by dissolving the resi- 
due remaining after all the ammonia has been driven off by careful 
heating, yields a beautiful reddish-violet color when a drop or two 
of a very dilute solution of sulphate of copper is added to its solu- 
tion alkalinized with sodium hydrate, this reaction maybe employed 
as a test in the detection of urea {Biuret Test). 

Urea is readily soluble in water, fairly so in alcohol, and insoluble 
in anhydrous ether and benzol. The aqueous solution of urea is 



THE URINE. 



297 



neutral in reaction, but combines with acids, bases, and salts to form 
molecular compounds. 

Of special interest are the compounds of urea with nitric acid, 
oxalic acid, and mercuric nitrate. Urea nitrate, CON 2 H 4 .HN0 3 , 



Fig. 78. 




Nitrate of urea crystals. (Krukenberg, after Kt)hne.) 

crystallizes in two different forms : in thin rhombic or six-sided col- 
orless plates, which are frequently observed arranged like shiugles 
one on top of the other when rapidly formed (Fig. 78), while larger 
and thicker rhombic columns or plates are obtained if the process of 




Oxalate of urea crystals. (Krukenberg, after KChne.) 



crystallization is allowed to proceed more slowly. Urea nitrate is 
readily soluble in distilled water, while in alcohol and water con- 
taining nitric acid it dissolves with difficulty. Upon heating it evap- 
orates without leaving a residue. Urea oxalate, CON 2 H 4 . C 2 H 2 4 , 



o^5 CLINICAL DIAGNOSIS. 

crystallizes in rhombic or six-sided prisms or plates (Fig. 79), which 
are less soluble in water than the nitrate : in alcohol and water con- 
taining oxalic acid it is only imperfectly soluble. With mercuric 
nitrate urea forms three different compounds, according to the con- 
centration of the two solutions, viz. . 0ON 2 H 4 Bg 2 NO a 4 . 0ON 2 H 4 , 
Hg 3 (XO ? f . and (OON 2 H 4 -.H. NO a g - 3HgO. The latter com- 
pound is of special importance, as Liebig's quantitative estimation of 
urea is based upon its formation. It results when a 2 per cent, 
solution of urea is treated with a dilute solution of mercuric nitrate. 
the reaction taking place according to the equation : 

. ; >N,H 4 - 4Hg NO s : - 3H : 0= [2 CO>~ ; H = , Hg NO* . - SHgO] - 6KN~0 3 . 

Very important is the behavior of urea when treated with a solu- 
tion of sodium hypochlorite or hypobromite, the most usual method 
of estimating urea being based upon this reaction, which may be 
represented by the equation: 

COX ; H 4 - SXaOBr = SN*Br - 2N - CO, - 2H.0. 

In the chapter on Reaction it was pointed out that urine when 
exposed to the air gradually undergoes ammoniacal fermentation, 
and that this decomposition is due to the action of a non-organized 
ferment, ammonia being liberated, according to the equation: 

: - HO = 2NH a - : 

m 

The same decomposition may be effected by heating a watery solution 
of urea in a sealed tube to 100° C. 

It might be supposed that an accurate estimation of urea could be 
made by adding a solution of the ferment, which can readily be 
obtained, to a known quantity of urine, and then determining the 
amount of ammonia liberated. 34 parts of the latter corresponding 
to 6C parts of urea. Unfortunately the complete decomposition 
of urea is obtained only with difficulty, so that the method is 
a very tedious one. The same objection, although to a less 
degree, can also be urged against the method commonly employed, 
viz.. the hypobromite method (which see), as 1 gramme of urea does 
not yield 372.7 c.c. of nitrogen, which would be theoretically re- 
quired, but at the most only 354.3 c.c. 

Separation of Urea from the Urine. From 50 to 100 c.c. of 
urine are evaporated to a syrupy consistence upon a water-bath, and 
extracted with 1( : 1 ; : strong alcohol, by rubbing up the 



THE URINE. 299 

residue while still hot with alcohol. Upon cooling, the mixture is 
filtered, the alcohol evaporated, and the residue treated with pure 
cold nitric acid. Urea nitrate then separates out either immediately 
or on standing. After twenty-four hours the crystalline mass is col- 
lected upon a muslin filter, well strained and freed from any liquid 
by placing it upon plates of clay. It is then dissolved in hot water, 
and the solution, if strougly colored, gently warmed with animal 
charcoal. This solution is neutralized with barium carbonate, and 
rendered alkaline with barium hydrate. The urea nitrate is thus 
decomposed, barium nitrate and urea being formed : 

2CON 2 H 4 .HN0 3 + BaC0 3 = 2CON 2 H 4 + Ba(N0 3 ) 2 + II 2 0. 
The barium is now removed by passing a stream of C0 2 through the 
solution and filtering off the precipitate. The filtrate is evaporated until 
any Ba(N0 3 ) 2 remaining crystallizes out. This is removed by decanta- 
tion, when upon further evaporation the urea will crystallize out, and 
may be dried between layers of filter-paper and recrystallized from 
95 to 98 per cent, alcohol. The crystals thus formed may now be 
subjected to further tests. To this end a few drops of an aqueous 
solution are added to a few c.c. of a sodium hypobromite solution, 
when in the presence of urea bubbles of gas will be given off. With 
a solution of sodium hypochlorite the same result may be obtained, 
but in this case the evolution of gas only takes place upon the appli- 
cation of heat. The formation of biuret may also be demonstrated 
by carefully melting a few of the crystals in a test-tube, dissolving the 
residue, when cool, in a little water, and alkalinizing the solution 
with a little sodium hydrate ; upon the addition of a drop or two of 
a dilute solution of sulphate of copper a beautiful reddish-violet 
color, owing to the presence of biuret, will develop. 

The addition of oxalic or nitric acid to a solution of urea will give 
rise to the formation of urea nitrate and oxalate, as described above. 

This latter test may very conveniently be made under the micro- 
scope : A drop of the concentrated solution is placed upon a slide 
and covered, and a drop of pure nitric acid added from the side. 
Crystals of urea nitrate will then be seen to separate out, and may 
be recognized by their characteristic shingle-like arrangement (see 
Fig. 78). 

"When a urine is very rich in urea the mere addition of nitric acid 
will cause a more or less abundant precipitation of urea nitrate, and 
with this simple test an idea may even be formed of the amount 
present pro liter. An appearance of hoar-frost is thus only noted 



300 CLINICAL DIAGNOSIS. 

when not less than 25 grammes are present to the liter, while the 
formation of spangles of urea nitrate requires the presence of at least 
45 grammes, and a heavy sediment is noted only when 50 grammes 
or more are present. 

Quantitative Estimation of Urea. The only method which 
will be considered in detail is the one based upon the decomposition 
of urea into carbon dioxide and nitrogen in the presence of sodium 
hypobromite, which reaction takes place according to the equation : 
CON 2 H 4 + 3NaOBr = NaBr + C0 2 + 2H 2 + 2N. 

The carbon dioxide thus formed is absorbed by an excess of sodium 
hydrate added to the hypobromite solution, while the nitrogen is set 
free, and can be suitably collected and measured, whence the determi- 
nation of the corresponding amount of urea becomes a simple matter. 
The only solution that is necessary is one of sodium hypobromite 
containing an excess of sodium hydrate. A 30 per cent, solution of 
the latter should be kept on hand and the sodium hypobromite solu- 
tion prepared when required. To this end 70 c.c. of the sodium 
hydrate solution are diluted with 180 c.c. of water and treated with 
5 c.c. of bromine in a bottle provided with a ground-glass stopper, 
the mixture being thoroughly shaken until every trace of free bro- 
mine has disappeared. Heat is evolved during this process and the 
mixture should not be used until cold. The sodium hypobromite 
solution, if kept in a perfectly dark and cool place, may be preserved 
for a week or two. The reaction which takes place between the 
sodium hydrate and the bromine may be represented by the equation: 

2NaOH + 2Br = NaBr + NaOBr + H 2 0. 

Various forms of apparatus, termed ureometers, have been suggested 
for the estimation of urea by this method. One which the author has 
found very satisfactory is represented in Fig. 80. It consists essen- 
tially of a burette, C, with an ascending rubber tube attached to the 
reservoir B, which can be raised or lowered as required for the purpose 
of equalizing the pressure, after the collection of the gas in the burette. 
A descending tube leads to a wide-mouthed bottle, A, containing the 
hypobromite solution. This is closed by a tightly fitting rubber 
stopper, to which a loop of platinum-wire is attached carrying a 
little bucket made of glass or porcelain, which can be swung from 
its support by inclining the bottle. 

Method: The rubber stopper is removed from the bottle A, and 
water poured into B until the system BCA is filled to such an 



THE URINE. 



301 



extent that the water-level is visible in B above the point where the 
rubber tube is attached. About 25 to 30 c.c. of the hypobromite solu- 
tion are then placed in the bottle A, 5 c.c. oi urine into the little 
bucket, and this attached to the wire loop. The stopper is then care- 
fully adjusted and the water in B and C brought to the same 
level, when the first reading is taken. A is then inclined until 
the little bucket drops into the liquid below. The nitrogen which 



Fig. 80. 




The author's ureometer. 



is^ liberated collects in the burette C, the water falling in C 
and rising in B. Ai'ter twenty to thirty minutes the pressure in 
C is equalized by lowering B until the water in both tubes has 
reached the same level. The second reading is then taken, the 
difference between the two indicating the volume of nitrogen liber- 
ated from 5 c.c. of urine at the temperature of the water in CB, 
which, as well as the barometric pressure, should be previously noted. 



302 CLINICAL DIAGNOSIS. 

As the volume of gases is greatly influenced by the temperature, 
the barometric pressure, and the tension of the aqueous vapor, it be- 
comes necessary, in order that the results reached shall be comparable 
with those obtaiued by other observers, to reduce the volume of 
nitrogen actually noted to a certain standard. This has been placed 
at 0° C. and 760 mercury millimetres pressure, in the absence of 
moisture. This correction is made according to the following formula : 

V= V ' ^ — , in which V represeuts the corrected vol- 

760.(1 + 0. 00366. t)' F 

ume of the gas in c.c, v the volume actually observed, B the barometric 
pressure in Hgmm., T the tension of the aqueous vapor at the tem- 
perature noted, t. The volume of nitrogen observed being thus 
corrected, the calculation of the corresponding amount of urea is 
based upon the following considerations : From the formula CON 2 H 4 
it is apparent that 2 atoms of nitrogen are contained in 1 molecule of 
urea; in other words, that 28 parts by weight of nitrogen correspond 
to 60 parts by weight of urea. The equivalent of 1 gramme of urea 
is then found according to the equation : 60 : 28 : : 1 : x, and x = 
0.46666. The volume corresponding to 0.4666 gramme of dry 
nitrogen at 0° C. and 760 Hgmm. pressure is 372.7 c.c. It has 
been found, however, that only 354.3 c.c. of nitrogen are evolved 
from 1 gramme of urea at best, when the hypobromite method is 
employed. Knowing that 354.3 c.c. of nitrogen correspond to 1 
gramme of ur^a, the amount of urea to which the volume of nitrogen 
actually observed is referable would then be found according to the 

equation: 1 : 354.3 : : x : y, and x = • — t — , in which y denotes the 
H J> 354.3' y 

number of c.c. of nitrogen evolved from 5 c.c. of urine, and x the 
corresponding amount of urea. In order to ascertain the percentage- 
amount of urea, it is only necessary to multiply the figure just 
obtained by 20. 

Precautions: 1. The urine must be free from albumin. 2. It 
should contain only about 1 per cent, of urea; i.e., not more than 
0.05 gramme in 5 c.c, corresponding to 17.715, to 20 c.c. of nitrogen. 
Whenever a greater amount is noted, therefore, the urine is diluted 
to the proper degree, allowance being made in the calculation. 

In ordinary clinical work the barometric pressure, as well as the 
tension of the aqueous vapor, may be neglected, and in the tables 
appended the corresponding amount of urea may be directly read off 
at the temperatures 5°, 10°, 15°, 20°, 25°, and 30° C. 



THE URINE. 303 

Urea. Table for a Temperature of 5° C. 





1 


Vio 


2 /io 


3 /io 


*/io 


6 /,0 


°/io 


T / 10 


B /l0 


°/io 


1 


1.32 


1.45 


1.58 


1.71 


1.S5 


1.98 


2.11 


2 21 


2.87 


2. .1 


2 


2.64 


2.77 


2.90 


3.03 


3.17 


3.30 


3.43 


3.56 


3 69 


3.83 


3 


3.96 


4.09 


4 22 


4.36 


4.49 


4.62 


l 75 


1.88 


5 02 




4 


5.2S 


5. 41 


5.51 


5.68 


5.81 


5.94 


6.07 


6.20 


6.34 


6,17 


5 


6.60 


6.73 


6.87 


7.00 


7.13 


7.26 


7.39 


7.53 


7.66 


7.79 


6 


7.92 


8.05 


8.19 


8.32 


8.45 


8.58 


S71 




8.98 


'.Ml 


7 


9.24 


9 38 


9.51 


9.61 


9.77 


9.90 


10.01 


10.17 


10 30 


10.43 


8 


10.56 


10.70 


10.83 


10.96 


11.09 


11.22 


11.36 


11.49 


11.62 


1 1 .75 


9 


11.89 


12.02 


12.15 


12.28 


12.41 


12.55 


12.68 


12. SI 


12.91 


18.07 


10 


13.21 


13 34 


13.47 


13.60 


13.73 


13.87 


14 00 


14.13 


14.26 


14.39 


11 


14.53 


14.66 


14.79 


14.92 


15.06 


15.19 


15.32 


15.45 


15.58 


15.72 


12 


15.85 


15.98 


16.11 


16.24 


16.38 


16.51 


16.64 


16.77 


16.90 


17 04 


13 


17.17 


17.30 


17.43 


17.57 


17.70 


17.83 


17.96 


18.09 


1323 


18.36 


14 


1S.49 


18.62 


18.75 


18 89 


19.02 


19.15 


19.28 


19.41 


19.55 


19.68 


15 


19. SI 


19.94 


20.08 


20.21 


20.34 


20.47 


20.60 


20.74 


20.87 


21.00 


16 


21.13 


21 26 


21.40 


21.53 


21.66 


21.79 


21.92 


22.06 


22.19 


22.32 


17 


22,45 


23 59 


22.72 


22.85 


22.98 


23.11 


23.25 


23.38 


23.51 


23.64 


18 


23.77 


23.91 


24.04 


24.17 


24.30 


24.43 


24.57 


24.70 


24.83 


24.96 


19 


25.10 


25.23 


25.36 


25.49 


25.62 


25.76 


25.89 


26.02 


26.15 


26.28 


20 


26.42 


26.55 


26.68 


26.S1 


26.94 


27.08 


27.21 


27.34 


27.47 


27.60 


21 


27.74 


27.87 


2S.00 


28.13 


28.27 


28.40 


28.55 


28.66 


28.79 


28.93 


22 


29.06 


29.19 


29.32 


29.45 


29.59 


29.72 


29.85 


29.98 


30.11 


30.25 


23 


30.38 


30.51 


30.64 


30.78 


30.91 


31.04 


31.17 


31.30 


31.44 


31.57 


24 


31.70 


31.83 


31.96 


32.10 


32.23 


32.36 


32.49 


32.62 


32.76 


32.89 


25 


33.02 


33.15 


33.29 


33.42 


33.55 


33.68 


33.81 


33 95 


34.08 


34.21 


26 


34.34 


34.47 


34.61 


34.74 


34.87 


35.00 


35.13 


35.27 


35.40 


35.53 


27 


35.66 


35.80 


25.93 


36.06 


36.19 


36.32 


36.46 


36.59 


36.72 


36.85 


28 


36.98 


37.12 


37.25 


37.38 


37.51 


37.64 


37.78 


37.91 


38 04 


38 17 


29 


3S.3L 


3S.44 


38.57 


38.70 


38.83 


38.97 


39.10 


39.28 


39.36 


39.49 


30 


39.63 


39.76 


39.89 


40.02 


40.15 


40.29 


40.42 


40.55 


40.68 


40.81 



Urea. Table for a Temperature of 10° C. 





1 


Vio 


2 /io 


3 /io 


4 /io 


5 /io 


6 /io 


7 /io 


8 /io 


9 /l0 


1 


1.30 


1.43 


1.56 


1.69 


1.82 


1.95 


2.08 


2.21 


2.34 


2.47 


2 


2.60 


2.73 


2.86 


2.99 


3.12 


3.25 


3.38 


3.51 


3.64 


3.77 


3 


3.90 


4.03 


4.16 


4.29 


4 42 


4.55 


4.68 


4.81 


4.94 


5.07 


4 


5.20 


5.33 


5.46 


5.59 


5.72 


5.85 


5.98 


6.11 


6.24 


6.37 


5 


6.50 


6.33 


6.76 


6.89 


7U2 


7.15 


7.28 


7.41 


7.54 


7.67 


6 


7.80 


7.93 


8.06 


8.19 


8.32 


8.45 


8.58 


8.71 


884 


8.97 


7 


9.10 


9.23 


9.36 


9.49 


9.62 


9.75 


9.88 


10.01 


10.14 


10.27 


8 


10.40 


10.53 


10.66 


10.79 


10.92 


11.05 


11.18 


11.31 


11.44 


1157 


9 


11.71 


11.84 


11.97 


12.10 


12.23 


12.36 


12.49 


12.62 


12.75 


12.88 


10 


13.01 


13.14 


13.27 


13.40 


13.53 


13.66 


13.79 


13.92 


14.05 


14.18 


11 


14.30 


14.41 


14.57 


14.70 


14.83 


14.95 


15.09 


15.22 


15 35 


15.48 


12 


15.60 


15.74 


15.87 


16.00 


16.13 


16.26 


16.39 


16.52 


16.65 


16.78 


13 


16.91 


17.04 


17.17 


17.30 


17.43 


17.56 


17.69 


17.82 


17.95 


18.08 


14 


18.21 


18.34 


18.47 


18.60 


18.73 


18.86 


18.99 


19.12 


19.25 


19 38 


15 


19.51 


19.64 


19.77 


19.90 


20.03 


20.16 


20.29 


20.42 


20.55 


20.68 


16 


20.81 


20.94 


21.07 


21.20 


21.33 


21.46 


21.59 


21.72 


21.85 


21.98 


17 


22.11 


22.24 


22.37 


22.50 


22.63 


22.76 


22.89 


23.02 


23.15 


23.28 


18 


23 41 


23.54 


23.67 


23.80 


23.93 


24.06 


24.19 


24.32 


24.45 


24.58 


19 


24.72 


24.85 


24 98 


25.11 


25.24 


25.37 


25.50 


25.63 


25.76 


25.89 


20 


26.02 


26.15 


26.28 


26.41 


26.54 


26.67 


26.80 


26.93 


27.06 


27.19 


21 


27.32 


27.45 


27.58 


27.71 


27.84 


27.97 


28.10 


28.23 


28 36 


28.49 


22 


28.62 


28.75 


28.88 


29.01 


29.14 


29.27 


29.40 


29.53 


29.66 


29.79 


23 


29.92 


30.05 


30.18 


30.31 


30.44 


30.57 


30.70 


30.83 


30.96 


31.09 


24 


31.22 


31.35 


31.48 


31.61 


31.74 


31.87 


32.00 


32.13 


32.26 


32.39 


25 


32.52 


32.65 


32.78 


32.91 


33.04 


33 17 


33.30 


33.43 


33.56 


33.69 


26 


33.82 


33.95 


34.08 


34.21 


34.34 


34.47 


34.60 


34.73 


34.86 


34.99 


27 


35.12 


35.25 


35.38 


35.51 


35.64 


35.77 


35.90 


36 03 


' 36.16 


36.29 


28 


36.42 


36.55 


36.68 


36.81 


36.94 


37.07 


37.20 


37.33 


37.46 


37.59 


29 


37.73 


37.86 


37.99 


38.12 


38.25 


38.38 


38.51 


38.64 


38.77 


38.90 


30 


39.03 


39.16 


39.29 


39.42 


39.55 


39.68 


39.81 


3 .94 


40.07 


40.20 



304 



CLINICAL DIAGNOSIS. 



Urea. Table for a Temperature of 15° C. 





1 


Vio 


2 /io 


3 /io 


4 /io 


5 /ao 


6 /io 


7 /io 


8 /io 


9 /io 


1 


1.28 


1.41 


1.53 


1.66 


1.79 


1.92 


2.04 


2.17 


2.30 


2.43 


2 


2.56 


2.69 


2.81 


2.94 


3,07 


3.20 


3.33 


3.46 


3.58 


3.71 


3 


3.84 


3.97 


4.10 


4.22 


4.35 


4.48 


4.61 


4.74 


4.87 


4 99 


4 


5.12 


5.25 


5.38 


5.50 


5.63 


5.76 


5.89 


6.02 


6.14 


6.27 


5 


6.40 


6.53 


6.60 


6.79 


6.91 


7.04 


7 17 


7.30 


7.43 


7.55 


6 


7.68 


7.81 


7.94 


8.07 


8.19 


8.32 


8.45 


8.58 


8.71 


8.83 


7 


8.96 


9.09 


9.22 


9.35 


9.48 


9.60 


9.73 


9.86 


9.99 


10.12 


8 


10.24 


10.37 


10.50 


10.63 


10.76 


10.88 


11.01 


11.14 


11.27 


11.40 


9 


11.53 


11.65 


11.78 


11.91 


12.04 


12.17 


12.29 


12.42 


12.55 


12.68 


10 


12.81 


12.93 


13.06 


13.19 


13.32 


13.45 


13.57 


13/.0 


13.83 


13.96 


11 


14.09 


14.22 


14.34 


14.47 


14.60 


14.73 


14.86 


14.98 


15.11 


15.24 


12 


15.37 


15.50 


15.62 


15.75 


15.88 


16.01 


16.14 


16.26 


16.39 


16.52 


13 


16.65 


16.78 


16.91 


17.03 


17.16 


17.29 


17.42 


17.55 


17.67 


17.80 


14 


17.93 


18.06 


18.19 


18.31 


18.44 


18.57 


18.70 


18.83 


18.95 


19.08 


15 


19.21 


19.34 


19.47 


19.60 


19.72 


19.85 


19.98 


20.11 


20.24 


20.36 


16 


20.49 • 


20.62 


20.75 


20.88 


21.00 


21.13 


21.26 


21.39 


21.52 


21.64 


17 


21.77 


21.90 


22.03 


22.16 


22.29 


22.41 


22.54 


22.67 


22.80 


22.93 


18 


23.05 


23.18 


23.31 


23.44 


23.57 


23.69 


23.82 


23.95 


24.08 


24.21 


19 


24.34 


24.46 


24.59 


24.72 


24.85 


24.98 


25.10 


25.23 


25.36 


25.49 


20 


25.62 


25.74 


25.87 


26.00 


26.13 


26.26 


26.38 


26.51 


26.64 


26.77 


21 


26.90 


27.03 


27.15 


27.28 


27.41 


27.54 


27.67 


27.79 


27.92 


28.05 


22 


28.18 


28.31 


28.43 


28.56 


28.69 


28.82 


28.95 


29.07 


29.20 


29.33 


23 


29.46 


29.59 


29.72 


29.84 


29.97 


30.10 


30.23 


30.36 


30.48 


30.61 


24 


30.74 


30.87 


31.00 


31.12 


31.25 


31.38 


31.51 


31.64 


31.76 


31.89 


25 


32.02 


32.15 


32.28 


32.41 


32.53 


32.66 


32.79 


32.92 


33.05 


33.17 


26 


33.30 


33.43 


33.56 


33.69 


33.81 


33.94 


34,07 


34.20 


34.33 


34.45 


27 


34.58 


• 34.71 


34.84 


34.97 


35.10 


35.42 


35.35 


35.48 


35.61 


35.74 


28 


35.86 


35.99 


36.12 


36.25 


36.38 


36.50 


36.63 


36.76 


36.89 


37 02 


29 


37.15 


37.27 


37.40 


37.53 


37.66 


37.79 


37.91 


38.04 


38.17 


38.30 


30 


38.43 


38.55 


38.68 


38.81 


38.94 


39.07 


39.12 


39 32 


39.45 


39.58 



Urea. Table for a Temperature of 20° C. 





1 


Vio 


2 /io 


3 /io 


4 /io 


5 /io 


6 /io 


7 /10 


8 /io 


9 /io 


1 


1.26 


1.38 


1.51 


1.63 


1.76 


1.89 


2.01 


2.14 


2.26 


2.39 


2 


2.52 


2.64 


2.77 


2.90 


3.02 


3.16 


3.27 


3.40 


3.53 


3.65 


3 


3.78 


3.91 


4.03 


4.16 


4.28 


4.41 


4.54 


4.66 


4.79 


4.91 


4 


5.04 


5.17 


5.29 


5.42 


5.54 


5.67 


5.80 


5.92 


6.05 


6.17 


5 


6.30 


6.43 


6.55 


6.68 


6.81 


6.93 


7.06 


7.18 


7.31 


7.44 


6 


7.56 


7.69 


7.81 


7.94 


8.07 


8.19 


8.32 


8.44 


8.57 


8.70 


7 


8.82 


8 95 


9.08 


9.20 


9.33 


9.45 


9.58 


9.71 


9.83 


9.96 


8 


10.08 


10.21 


10.34 


10.46 


10.59 


10.71 


10.84 


10.97 


11.09 


11.22 


9 


11.35 


11.47 


11.60 


11.72 


11.85 


11.98 


12.10 


12.23 


12.35 


12.48 


10 


12.61 


12.73 


12.86 


12.98 


13.11 


13.24 


13.36 


13.49 


13.61 


13.74 


11 


13.87 


13.99 


14.12 


14.25 


14.37 


14.50 


14.62 


14.75 


14.88 


15.00 


12 


15.13 


15.25 


15.38 


15.51 


15.63 


15.76 


15.88 


16.01 


16.14 


16.26 


13 


16.39 


16.52 


16.64 


16.77 


16.89 


17.02 


17.15 


17.27 


17.40 


17.52 


14 


17 65 


17.78 


17.90 


18.03 


18.15 


18.28 


18.41 


18.53 


18.66 


18.78 


15 


18.91 


19.04 


19.16 


19.29 


19.42 


19.54 


19.67 


19.79 


19.92 


20.05 


16 


20.17 


20.30 


20.42 


20.55 


20.68 


20.80 


20.93 


21.05 


21.18 


21.31 


17 


21.43 


21.56 


21.69 


21.81 


21.94 


22.06 


22.19 


22.32 


22.44 


22.57 


18 


22.69 


22.82 


22.95 


23.07 


23.20 


23.32 


23.45 


23.53 


23.70 


23.83 


19 


23.96 


24.08 


24.21 


24.33 


24 46 


24.59 


21.71 


24.84 


24.96 


25.09 


20 


25.22 


25.34 


25.47 


25.59 


25.72 


25.85 


25.97 


26.10 


26 22 


26.35 


21 


26.48 


26.60 


26.73 


26.86 


26.98 


27.11 


27.23 


27.36 


27.49 


27.61 


22 


27.74 


27.86 


27.99 


28.12 


28.24 


28.37 


28.49 


28.62 


28.75 


28.87 


23 


29.00 


29.13 


29.25 


29.38 


29.50 


29.63 


29.76 


29.88 


30.01 


30.13 


24 


30.26 


30.39 


30.51 


30.64 


30.76 


30.89 


31.02 


31.14 


31.27 


31.39 


25 


31.52 


31.65 


31.77 


31.90 


32.03 


32.15 


32.28 


32.40 


32.53 


32.66 


26 


32.78 


32.91 


33.03 


33.16 


33.29 


33.41 


33 54 


33.66 


33.79 


33.92 


27 


34,04 


34.17 


34.30 


34.42 


34.55 


34.67 


34.80 


34.93 


35.05 


35.18 


28 


35.30 


35.43 


35.56 


35.68 


35.81 


35.93 


36.06 


36.19 


36.31 


36.44 


29 


36.57 


36.69 


36.82 


36.94 


37.07 


37 20 


37.32 


37.45 


37.57 


37.70 


30 


37.83 


37.95 


38.08 


38 20 


38.33 


38.46 


38.58 


38.71 


38.83 


38.96 



THE UBIXK 



305 



Urea. Table for a Temperature of 25° C. 








Vio 


2 /io 


S /l0 


4 / 10 


6 /io 


6 /io 


7 /io 


8 /io 


■',., 


1 


1.24 


1.36 


1.49 


1.61 


1.73 


1.86 


1.98 


2.11 


2.23 


2.85 


2 


2.48 


2.60 


2.73 


2.85 


2 97 


3.10 


8.22 


3.35 


3.47 


8.59 


3 


3.72 


3.84 


3.97 


4 09 


4.22 


I.:; 1 


L46 


I..V.1 


4.71 


4.84 


4 


4.96 


5.08 


5.21 


5.33 


5.46 




5.70 


5.83 




6. lis 


5 


6.20 


6.33 


6.45 


6.57 


6.70 


6.82 


6.95 


7.07 


7.19 


7.32 


6 


7.44 


7.57 


7.69 


7.81 


7.94 


8.06 


8.19 


8.31 


8.43 


8.50 


7 


8.68 


8.81 


8.93 


9.06 


9.18 


9.30 


9.43 


9.55 


9.68 


9.80 


8 


9.92 


10.05 


10.17 


10.30 


10.42 


10.54 


10.67 


10.79 


10.92 


10.04 


9 


11.17 


11.29 


11.41 


11.54 


11.66 


11.79 


11.91 


12 03 


12.16 


12.28 


10 


12.41 


12.53 


12.65 


12.78 


12.90 


13.03 


13.15 


13.27 


13.40 


13.52 


11 


13.65 


13.77 


13.89 


14.02 


14.14 


14.27 


14.39 


14.52 


14.64 


14.76 


12 


14.89 


15.01 


15.14 


15.26 


15.38 


15.51 


15.63 


15.76 


15.88 


16.00 


13 


lti. 13 


16.25 


16. 38 


16.50 


16.63 


16.75 


16.87 


17.00 


17.12 


17.26 


14 


17.37 


17.49 


17.62 


17.74 


17.87 


17.99 


18.11 


18.24 


18.36 


18.49 


15 


18.61 


18.74 


18.86 


18.98 


19.11 


19.23 


19.36 


19.48 


19.60 


19.73 


16 


19.85 


19.98 


20.10 


20.22 


20.35 


20.47 


20.60 


20.72 


20.84 


20.97 


17 


21.09 


21.22 


21.34 


21.47 


21.59 


21.71 


21.84 


21.96 


22.09 


22.21 


18 


22.33 


22.46 


22.58 


22.71 


22.83 


22.95 


23.08 


23.20 


23.33 


23.45 


19 


23.58 


23.70 


23.82 


23.95 


24.07 


24.20 


24.32 


24.44 


24.57 


24.69 


20 


24.82 


24.94 


25.06 


25.19 


25.31 


25.44 


25.56 


25.68 


25.81 


25.93 


21 


26.06 


26.18 


26.30 


26.43 


26.55 


26.68 


26.80 


26.92 


27.05 


27.17 


22 


27.30 


27.42 


27.55 


27.67 


27.79 


27.92 


28.04 


28.17 


28.29 


28.41 


23 


28.54 


28.66 


28.79 


28.91 


29.04 


29.16 


29.28 


29.41 


29.53 


29.66 


24 


29.78 


29.90 


30.03 


30.15 


30.28 


30.40 


30.52 


30.65 


30.77 


30.90 


25 


31.02 


31.15 


31.27 


31.39 


31.52 


31.64 


31.77 


31.89 


32.01 


32.14 


26 


32.26 


32.39 


32.51 


32.63 


32.76 


32.88 


33.01 


33.13 


33.25 


33.38 


27 


33.50 


33.63 


33.75 


33.88 


34.00 


34.12 


34.25 


34.37 


34.50 


34.62 


28 


34.74 


34.87 


34.99 


35.12 


35.24 


35.36 


35.49 


35.61 


35.74 


35.86 


29 


35.99 


36.11 


36.23 


36.36 


36.48 


36.61 


36.73 


36.85 


36.98 


37.10 


30 


37.23 


37.35 


37.47 


37.60 


37.72 


37.85 


37.97 


38.09 


38.22 


38.24 



Urea. Table for a Temperature of 30° C. 








Vio 


2 /io 


3 /io 


4 /io 


5 /io 


6 /io 


7 /io 


8 /io 


9 /io 


1 


1.22 


1.34 


1.46 


1.58 


1.71 


1.83 


1.95 


2.07 


2.19 


2.32 


2 


2.44 


2.56 


2.68 


2.80 


2.93 


3.05 


3.17 


3.29 


3.41 


3.54 


3 


3.66 


378 


3.90 


4.03 


4.15 


4.77 


4.39 


4.51 


4.64 


4.76 


4 


4.88 


5.00 


5.12 


5.25 


5.37 


5.49 


5.61 


5.73 


5.86 


5.93 


-5 


6.10 


6.22 


6.35 


6.47 


6.59 


6.71 


6.83 


6.96 


7.08 


7.20 


6 


7.32 


7.44 


7.57 


7.69 


7.81 


7.93 


8.05 


8.18 


8.30 


8.42 


7 


8.54 


8.67 


8.79 


8.91 


9.03 


9.15 


9.28 


9.40 


9.52 


9.64 


8 


9.76 


9.89 


10.01 


10.13 


10.25 


10.37 


10.50 


10.62 


10.74 


10 86 


9 


10.99 


11.11 


11.23 


11.35 


11.47 


11.60 


11.72 


11.84 


11.96 


12.08 


10 


12.21 


12.33 


12.45 


12.57 


12.69 


12.82 


12.94 


12.06 


13.18 


13.30 


11 


13.43 


13.55 


13.67 


13.79 


13.92 


14.04 


14.16 


14.28 


14.40 


14.53 


12 


14.65 


14.77 


14.89 


15.01 


15.14 


15.26 


15.38 


15.50 


15.62 


15.75 


13 


15.87 


15.99 


16.11 


16.24 


16.36 


16.48 


16.60 


16.72 


16.85 


16.97 


14 


H- 09 


17.21 


17.33 


17.46 


17.58 


17.70 


17.82 


17.94 


18.07 


18.19 


15 


£ 31 


18.43 


18.56 


18.68 


18.80 


18.92 


19.04 


19.17 


19.29 


19.41 


16 


l%' oS 


19.65 


19.78 


19 90 


20.02 


20.14 


20.26 


20.39 


20.51 


20.63 


17 


20.75 


20.88 


21.00 


21.12 


2124 


21.36 


21.49 


21.61 


21.73 


21.85 


18 


ol 97 


22.10 


22.22 


22.34 


22.46 


22.58 


22.71 


22.83 


22.95 


23.07 


19 


o?-l 9 


23.32 


23.44 


23.56 


23.68 


23.81 


23.93 


24.05 


24.17 


24.29 


20 


24 49 


24.54 


24.66 


24.78 


24.90 


25.03 


25.15 


25.27 


25.39 


25.51 


21 


£«5 


25.76 


25.88 


26.00 


26.13 


26.25 


26.37 


26.49 


26.61 


26.74 


22 


oq-86 


26.98 


27.10 


27.22 


27.35 


27.47 


27.59 


27.71 


27.83 


27.96 


23 


™-08 


28.20 


28.32 


28.45 


28.57 


28.69 


28.81 


28.93 


29.06 


29.18 


24 


on-30 


29.42 


29.54 


29.67 


29.79 


29.91 


30.03 


30.15 


30.28 


30.40 


25 


2?.52 


30.64 


30.77 


30.89 


31.01 


31.13 


31.25 


31.38 


31.50 


31.62 


26 


S.74 


31.86 


31.99 


32.11 


32.23 


32.35 


32. 17 


32.60 


32.72 


32.84 


27 


o7 96 


33.09 


33.21 


33.33 


33.45 


33.57 


33.70 


33.82 


33.94 


34.06 


28 


51 18 


34.31 


34.43 


34.55 


34 67 


34.79 


34.92 


35.04 


35.16 


35.28 


29 


Sii 


35.53 


35.65 


35.77 


35.89 


36.02 


36.14 


36.26 


36.38 


36.50 


30 


36 :63 


36.75 


36.87 


36.99 


37.11 


37.24 


37.36 


37.48 


37.60 


37.72 



20 



306 



CLINICAL DIAGNOSIS. 



Fig. 81. 



O! the other forms of apparatus, the ureometers devised by Dore- 
mus, Green, Marshall, Hliffner, and Squibb may be mentioned. 
Dor anus's apparatus (Fig. 81) consists of a tube bent at an angle of 
45°, its long arm being closed and graduated, while 
the shorter arm is open and ends in a bulb. The 
apparatus is filled with the sodium hypobromite 
solution, when 1 c.c. of urine, diluted to the 
proper degree (see above), is carefully introduced 
by means of the accompanying pipette, the urine 
being allowed to leave the pipette very gradually, 
so that a loss of gas is obviated. After all bub- 
bles of gas have disappeared the reading is taken. 
The degrees marked upon the tube indicate directly 
the number of grammes or grains of urea con- 
tained in 1 c.c. of urine. Accuracy cannot, of 
course, be expected from this apparatus, but the 
results obtained are sufficiently exact for clinical 
purposes. 1 

Green's apparatus (Fig. 82) consists of a tube 
graduated in c.c, and blown out at the bottom 
into a wider portion, holding about 50 to 60 c.c. 
The bulb is provided with a side-tube, into which 
a bent funnel-tube can be inserted for the purpose of equalizing the 
pressure. The side-tube having been detached, the apparatus is filled 
with sodium hypobromite solution, when 2 c.c. of urine, diluted if 
necessary, are introduced by means of a graduated and bent pipette. 
After all bubbles of gas have disappeared the funnel-tube is inserted 
into the side-opening and filled with hypobromite solution until the 
level in both tubes is the same. The volume is then noted, corrected, 
and the corresponding amount of urea calculated as described. 

Marshall's apparatus is a conveniently modified form of Green's, 
and is used in the same manner (Fig. 83). 

Hiiffner's apparatus is excellent (Fig. 84). It consists of a small 
bulb, A, of 5 c.c. capacity, which is separated from a larger bulb, 

C, holding about 100 c.c, by a well-oiled glass stopcock. The upper 
end of C is drawn out to such an extent that the eudiometer 

D, which is about 30 cm. long, 2 cm. wide, and divided into fifths 

1 Instead of employing the solution described on page 300, it is sufficient to fill the long 
arm of the tube with a solution containing 100 grammes of caustic soda dissolved in 250 c.c. 
of distilled -water, and to add 1 c.c. of bromine and a sufficient amount of water to fill the 
bend of the tube. 




Doremus's ureometer. 



THE URINE. 



307 



of c.c, can be passed over it for a short distance. The bowl E, 
fitted over C by means of a cork, serves to hold a portion of the 
hypobromite solution. 

The exact capacity of A and of the lumen of the stopcock must 
be separately determined for each instrument. 

Method: The bulb A and the lumen of the stopcock are filled 
with urine which has been diluted, if necessary. The stopcock 
having been closed, C is washed out carefully with distilled water 
and filled with the hypobromite solution until the liquid in the 



Fig. 82. 



Fig. 83. 



Fig. 84. 





Green's ureometer. 



Marshall's ureometer. 



Hiiflner's ureometer. 



dish stands several cm. above the mouth of C. The eudiometer 
is next filled with the same solution and carefully submerged in the 
liquid contained in the dish, adjusted over the mouth of C. The 
urine in A is then allowed to mix with the hypobromite solution 
very gradually by opening the stopcock. After all bubbles of gas 
have disappeared the eudiometer is transferred to a cylinder filled 
with water and thoroughly immersed. After twenty to thirty min- 
utes the level of the liquid in the tube and that of the outside water 
are equalized and the reading taken. The temperature of the water 



308 



CLIXICAL DIAGXOSIS. 



being: likewise noted, the volume of the g;as is corrected and the 
corresponding amount of urea calculated. 

Squibb' s method: This method, as well as that of Doreinus, may 
be highly recommended to the practitioner for its simplicity. The 
apparatus (Fig. 85) consists of two ordinary medicine-bottles, A 
and B, A being the one in which the nitrogen is evolved. B 
is closed by a doubly perforated rubber-stopper, a straight tube 
passing through the upper aperture and connectiug with the bottle 
A Another tube, bent downward and carrying a clamp, as seen 
in the figure, leads to a graduated cylinder, E. B contains a 
sufficient amount of water for the bent tube to dip into ; 25 to 30 
c.c. of the hypobromite solution, and a small tube containing 5 
c.c. of urine, diluted if necessary, according to the specific gravity, 
are placed in A, the clamp at E being closed. The rubber- 
stopper is now firmly inserted aud E opened, when a few drops 



Ete. c :. 




Squibb' s ureometer. 



of water, which may be disregarded, will escape. The graduated 
cylinder is then placed beneath the outflow-tube and the bottle A 
inclined. The nitrogen collecting in B displaces its own volume 
of water, which flows out and is collected in C, whence the corre- 
sponding amount of urea may be calculated. 

It should be mentioned that sodium hypobromite liberates nitro- 
gen, not only from the urea, but also from the other nitrogenous con- 
stituents of the urine ; the error thus incurred, however, appears 
just to counterbalance the deficit in the amount of nitrogen obtained, 
corresponding to 1 gramme of urea. 



THE URINE. 



309 



Estimation of Nitrogen. Whenever it becomes necessary, as in 
accurate experiments on metabolism, to estimate the total quantity 
of nitrogen the following method may be conveniently employed : 

Principle : If nitrogenous organic material is heated in intimate 
contact with a mixture of calcic soda (Natronkalk), all the nitrogen 
is given off in the form of ammonia, which latter is collected in a 
known quantity of acid ; the excess not used in the neutralization 
of the ammonia is then determined by titration with a solution of 
sodium hydrate of known strength. The amount held by the am- 
monia is thus ascertained, and from it the corresponding amount 
of nitrogen, it being remembered that 17 grammes of ammonia cor- 
respond to 14 grammes of nitrogen. 

Reagents required : 1. A quantity of thoroughly fused calcic soda, 
which, while still hot, should be placed in a well-stoppered bottle, 
where it may be kept ready for use for a long time. 

2. A normal solution of sulphuric acid. 

3. A normal solution of sodium hydrate. 

e Fig. 86. 




Apparatus for the determination of nitrogen. 

Apparatus required : As is apparent from the accompanying dia- 
gram (Fig. 86), the apparatus consists of a small flask, A, with a long 
neck (10 to 12 cm. long), of about 100 c.c. capacity, which is placed 



310 CLINICAL DIAGNOSIS. 

in a copper crucet, B, and imbedded in sand. The crucet is placed 
upon a pipe-stem triangle over the flame. The neck of the flask is sur- 
rounded by a hood of copper or iron plate, C, moulded to the flask 
and reaching not higher than 1.5 cm. below the rubber-stopper. The 
latter is doubly perforated, a tube drawn out to a point and closed 
at the free end passing through one aperture and extending about 
half-way down the flask, while the second passes through the other 
opening. This second tube, c, is connected by means of a short piece 
of rubber-tubing, upon which a clamp is placed with a Will and 
Tarrentrapp's apparatus. The latter is connected by rubber-tubing, 
upon which a clamp is placed, with an aspirating-bottle filled with 
water, into which a siphon, provided with a rubber-tube at its free 
end, dips to the bottom. 

Method: Ten c.c. of the normal sulphuric-acid solution are placed 
in the Will and Tarrentrapp's apparatus together with a few c.c. of 
a 1 per cent, solution of phenolphthalein. A layer of sand about 1 
cm. in height is placed in the crucet, the clamp a closed, and the 
flask filled to about one-half its height with calcic soda, when the 
hood is adjusted and 5 c.c. of urine allowed to flow upon the soda. 
The rubber-stopper is quickly adjusted, the rubber tube having been 
previously connected with the Will and Tarrentrapp's apparatus and 
aspirating-bottle. The clamp a is now opened, the crucet filled up 
with sand, and the heating begun. This is at first doue carefully 
with a small flame, but increased gradually until a full heat is ap- 
plied. This is continued for one-half to three-quarters of an hour. 
When drops of moisture are no longer visible in the tube c, or 
when the evolution of gas has entirely ceased, the rubber tube of the 
aspirating-bottle d is slipped on to the Will and Tarrentrapp's 
apparatus, the clamp b slightly opened, the tip of e broken off, 
and air allowed to pass slowly through the entire system for a 
quarter of an hour, when the flame is extinguished, the Will and 
Tarrentrapp's apparatus detached, and its contents titrated with the 
normal solution of sodium hydrate. 

The number of c.c. of the sodium hydrate solution employed is 
deducted from 10 (the number of c.c. of the normal sulphuric-acid 
solution, 1 c.c. of the latter being equivalent to 1 c.c. of the former), 
the difference giving the number of c.c. of the normal sulphuric-acid 
solution neutralized by the ammonia evolved from 5 c.c. of urine. 
This number multiplied by 20 will then represent the number of 
c.c. required to neutralize the ammonia contained in 100 c.c. of 



THE URINE, 31] 

uriue. As 1000 c.c. of the normal solution of sulphuric acid cor- 
respond to 17 grammes of ammonia or 14 grammes of nitrogen, 
the number of c.c. of the sulphuric-acid solution corresponding to 
100 c.c. of urine will be found from the equation: 1000: 14: : x : y, 

and y= . in which x represents the number of c.c. required 

to neutralize the amount of ammonia evolved from 100 c.c. of urine 
and y the corresponding amount of nitrogen — i. e. } the percentage of 
nitrogen. 

If the nitrogen is to be calculated in terms of urea, this is done 

according to the equation : 1000 : 30 ( = 14N) : : x : y, and y = 3Qx 

= percentage of urea, in which x represents, as above, the number 
of c.c. of sulphuric acid neutralized by the ammonia, viz., nitrogen, 
contained in 100 c.c. of urine, and y the urea corresponding to this 
amount. 

Uric Acid. 

Uric acid was formerly regarded as an antecedent of urea, a view 
which has gradually been abandoned, however. Urea, if derived 
from uric acid at all, is certainly so derived only to a very limited 
extent. 

In the case of birds the researches of Minkowski, v. Schroeder, 
and others seem to point to an origin of uric acid analogous to that 
of urea in mammals, a great decrease in the elimination of this sub- 
stance having been observed following extirpation of the liver in 
geese, associated with a corresponding increase in the excretion of 
ammonia, and with this of lactic acid. In birds, at least, its forma- 
tion from these two substances by a process of synthesis would, 
hence, appear very probable. Since amido-acids, such as leucin, 
glycocoll, and asparaginic acid, produce an increased elimination of 
uric acid in birds, the origin of the ammonia from these substances 
might as well be supposed to be the same here as in the case of 
the formation of urea in mammals. 

In the latter class, according to our present knowledge, the nucle- 
ins contained in the nuclei of cells must be regarded as the most 
probable antecedents of uric acid, a supposition to which not only 
the facts presently to be considered, but also the chemical relation 
which exists between these bodies points (see below). The spleen has 
thus recently been suggested as the most probable seat of the forma- 
tion of uric acid, and the fact that an increased elimination is ob- 



312 CLINICAL DIAGNOSIS. 

served in cases of splenic hypertrophy, and that this diminishes as 
the size of the organ diminishes under the administration of qui- 
nine, must be considered as a strong support of this hypothesis. The 
observations of Horbaczewski, moreover, who noted a decided new 
formation of uric acid when blood of calves and splenic pulp were 
allowed to stand in contact in the presence of oxygen, appear to 
render the splenic origin of this substance still more probable. The 
leucocytes are thought to be especially concerned in this transforma- 
tion, and, as a matter of fact, it is known that the amount of uric 
acid is increased in cases of splenic leukaemia and during the process 
of digestive leucocytosis. 

Uric acid, which is almost insoluble in water, is held in solution 
in the urine in consequence of the presence of disodium phosphate, 
which transforms it into the readily soluble neutral disodium urate, 
according to the following equation : 

2N£4HP0 4 + C 5 H 4 :N T 4 3 = 2NaH 2 P0 4 + C 5 H 2 Xa.>\0 3 . 

Should uric acid be present in larger amount, the disodium urate 
gives up part of its sodium, acid monosodium urate resulting, which, 
being soluble only with difficulty, is thrown down in concentrated 
urines as a sediment. The reaction taking place is represented by 
the following equation : 

C 5 H 4 N 4 3 -f C 5 H 2 Na 2 N 4 3 = C 5 H 3 NaN 4 O s + C 5 H 3 XaN 4 3 . 

Should a still greater amount of uric acid be present, this is 
thrown down as such. The normal amount of uric acid excreted in 
the twenty-four hours may be said to vary between 0.2 and 1 gramme, 
being influenced to a certain extent by the character of the food, a 
diet rich in nitrogenous material increasing the amount of uric acid, 
while a diminished elimination of uric acid results from a diet free 
from nitrogen. It is also influenced by the amount of exercise taken, 
diminishing during rest and increasing with muscular activity. In 
addition, there are certain individual peculiarities, of the nature of 
which, however, practically nothing is known. Hence it has always 
been held that it is impossible in many cases to state definitely 
whether the amount of uric acid excreted by an individual is normal 
or not, as the tolerance on the part of the body of this substance varies 
greatly in different persons. 

The relation normally existing between the excretion of uric acid 
and of urea has been placed at between 1 : 50 and 1 : 60, but is 
inconstant, especially in pathologic conditions, in which the relative 
amount of uric acid may be greatly increased. It is impossible at 



THE UBINE. 313 

the present time to furnish a satisfactory explanation of the varia- 
tions in the excretion of nric acid observed in pathologic conditions, 
and but little more, in fact, can be done than to enumerate the vari- 
ous diseases in which such variations have been observed. 

In febrile diseases, as typhoid fever, pneumonia, pleurisy, peri- 
carditis, etc., the excretion of uric acid appears to be quite constantly 
increased. 

Very interesting and suggestive are the data obtained in cases 
of true leukaemia, in which a daily excretion of from 1 to 5 grammes 
is frequently observed. The relation existing between the elimination 
of uric acid and of urea may here vary from 1 : 45 to 1 : 19, or even 
1:12. In a few cases of pseudo-leukaemia a like increase has been 
noted. In one case which the author had occasion to study for about 
three weeks the actual amount eliminated varied between 0.256 and 
0.957 gramme, while the relation between it and urea varied from 
1 : 64 to 1 : 22. In general it may be said that the elimination of 
uric acid is increased in all splenic diseases. In pernicious anaemia 
the uric acid was found to be normal or increased. In dyspeptic 
disturbances the uric acid is frequently increased. In hepatic cir- 
rhosis the relation of uric acid to urea has been found to vary from 
1: 19 to 1 : 38, while the amount of the former varied between 0.5 
and 2 grammes. 

An increased elimination of uric acid, forming a disease sui generis, 
as it were, must also be noted, constituting the so-called uric-acid 
diathesis, in which au enormous increase in the elimination of this 
substance appears to constitute the only objective symptom. Pa- 
tients thus afflicted are the subjects of profound hypochondriasis 
and lose flesh rapidly. 

Da Costa has recently described a condition which is characterized 
by the existence of certain nervous symptoms, such as listlessness, 
fatigue upon slight exertion, headache, despondency, giddiness, and 
sleeplessness, associated with an elimination of a trace of albumin, 
large amounts of uric acid, oxalic acid, or both. Cardiac hyper- 
trophy and other cardiac lesions of Bright's disease were conspic- 
uously absent. The specific gravity in such cases is always high, 
varying between 1.022 and 1.036. The quantity of urine is about 
normal. The author has noted a considerable increase in the amount 
of urea in such cases. 

The excretion of uric acid in gout has been the subject of numerous 
investigations, and while the causes producing the variations here 



; :-_4 ;:;y;:i: ~_i ;-:\" *ii 

observed are still a matter of great uncertainty, a diminished elim- 
ination in the chronic state of the disease, especially marked im- 

... "..;:r'.~ -.-■_ ■■-:- ./i^ :'i- :•:•.; 'irrri::^ :: :::::::::.:•. :-~:.- : ; in 
:z ■■; ■;; — '". r'.i-iii:::: : '::ii' in:: :iZ:':;;::c.j :::-: in i::i :k. niir ;e 
■_.''-... = :: :' ::s. i:^:. : :_ ::.:: \: ::: :.:;;•- 
ited in the form of tophi, in consequence of an increased degree of 
i"i:.i":i:~ : : t : L :■■:.::. " : - " :ri ._r:. ii :if :;; :sr :: ;• : ;:i i~i ;n~. 
:.:.t .. : : . ~ ;/.— :_:.. ::: .-.::. i-rnrrSS'' : - ::i:. "- I i: : .-.--. : ir- -~~z 
t.: ■'..•::- : . :j :"_t - ;. ~ :.t1 n;;i;.:_ :: :'nf -;-:t._. i~ :: -—-. — ::;. -.::•; : 
acid. Whether or not we are dealing with a process of increased 
-.::::'.:.:: :;n :: :: ::. i-ini-i^i r.iniini:: : 1 :: :i:s ; ::-::.::: :n ^..:: 
riiniin- : c ;~~t: :: ": -_ :^:\\-- r :. 

In diabetes a diminished amount of uric acid is usually found. 
CiScS —:i~ br — ■-.:.. _;~ 7 -ri". in ~::_:n. iss: ;::.:-:: —in: 1 ;:;:n:n\::;;n 
in ::iiTib:7i:^::e :: «:^:, :.:-;-: :■■;:::? a ^:«: ^::i:^i ii::^-: 
in :_t iniym: :: .:::: ; :■: . in:: _:i:;_^ in »■: iir ii-s-rs :■" ■! ^rinims : ■: 
.: :. T; :ni~ vi::r!:: :ir r-rrn: ; :'-:'-:■ :.'-/■• ■-..* nis ':; ^- itp".->::. 

In the ordinary forms of ansemia and chlorosis the amount of 
nri: ;:::: is rihe /-insninnij ;::l:;_;~i-.:. S<: i'.=.: in ;i::;ni; ii.frsri- 
tial nephritis, chronic lead-poisoning, progressive muscular atrophy, 
m;: ~-rT"i:: >'.".~"'t:-:: mi: 11 7*2". 7=:.= . 

Very interesting and suggestive is the increased elimination ob- 
; 7.':-t-:. in i:n:c i.:.:/ii"; :ninz:i:is:i. ririni::^ :: n;:n::i :: r'.'f: 
":r:: nin^ »n:n;:;:nii. ~i:n ::' 1: : ;. .:_.zi' ;::Ti:i>::c. 

J::- m;: ;•; ii--\;_i; ;i 1 — ?..z :z::^.-z-i ri.in:i::i:i:n ;: uri: i:i;I. 
^~i:i 1 vr^:!e ii-: rn : 1 7— i- -z\:r:ri :im — ::i: in miniil 7-:. 
I: j :a-c :::v/:j3:::t i. "I": ^rinnir —1.5 :ins n::ei — ;:ii ::^ fir- 
mer diet, as compared with 1.398 grammes with the lat 

I: : ; . :::- ::::';m:::---7-: ::-ir: :::•: :-:.ri: :ir »i:;e:: :; 
the so-called uric-acid diathesis a diet containing as small an amount 
of nitrogenous material, particularly of animal origin, as possible. 
- :■:•!; :.;_ in i.niiiiT ~i.:= :_n inii :;:-•::. s;:_ is n;:i-:-is. :ir 
more acid fruits, and berries. Cheeses should be avoided, being 
rich in albumins and very poor in alkaline salts. The reverse, of 
course, holds good when for any reason an increased elimination of 
uric acid appears advisable, the main factor to be considered in each 
case being the degree of alkalinity of the blood. Recently it has 
' '--- - . "~:: :::i: :_::::.: :- in; ;::.- ;: ;..; i;i;~; i:- ::;: : : r ;; nil-: 
a diet rich in nucleins, thymus having been employed in the cases 
; ^-r' : :-:. 



THE URINR 315 

Of drugs, salicylic acid and its salt-, as well as disodium phosphate, 
increase the elimination of uric acid. Alkalies, on the other hand, 
are indicated when an excessive excretion exists, and the same may 
be said of potassium iodide, quinine, antipyrin, thallin, etc. 

Steam baths cause a most decided increase, amounting in some 
cases to twice or thrice the normal amount, the increase often persist- 
ing for several days. 

Properties of Uric Acid. Chemically uric acid is closely related 
to urea on the one hand, and to the xanthin-bases on the other. Its 
relation to urea is quite clear, if it be remembered that oxidizing 
agents transform uric acid into urea or into substituted ureas, such 
as allantoin and alloxan, which latter is closely related to parabanic 
acid, or oxalyl urea, and barbituric acid, or malonyl urea. 

The relation existing between these various substances is seen in 
the following equations : 

1. C 5 H 4 X 4 3 + H,0 + O = C 4 H«N 4 + C0 2 . 
Uric acid. Allantoin. 

2. C 5 H 4 N 4 3 + H 2 - O = C 4 H 2 N 2 4 + CON 2 H 4 . 
Uric acid. Alloxan. Urea. 

3. C 4 H,X 2 4 + O = C 3 H 2 N 2 3 + C0 2 . 

Alloxan. Parabanic acid. 

The relation existing between uric acid and the xanthin-bases is 

seen from the following formula? : 

Hypoxanthin ......... C 5 H 4 N 4 

Xanthin C 5 H 4 N 4 O a 

Uric acid C 5 H 4 N 4 O s 

Guanin C 5 H 5 X 3 

As a matter of fact, it is possible to produce xanthin aud hypoxanthin 
from uric acid by a process of reduction. 

Uric acid forms a white crystalline powder which is almost insolu- 
ble in cold water (1 : 14000), difficultly soluble in boiling water 
(1 : 1800), and insoluble in alcohol and ether. In concentrated sul- 
phuric acid it readily dissolves, but is precipitated upon dilution with 
water. In aqueous solutions of the alkaline carbonates and hydrates 
it dissolves with the formation of acid — viz., neutral — salts, as rep- 
resented in the following equations : 

C 5 H 4 N 4 3 + Na 2 C0 3 = C 5 H 3 XaN 4 3 + NaHCO s . 
C 6 H 4 N 4 3 -f 2NaOH = C 5 H 2 Xa 2 NA + H 2 0. 

In the urine the amount of water present would not be sufficient 
to hold the uric acid in solution, this being accomplished by the 
disodium phosphate, as pointed out above. 



o : CLINICAL DIAGNOSIS. 

acid is found in the mine in the form of sodium, potassium. 

and ammonium salts, traces of calcinm and magnesium compounds 

being possibly also present. These salts may be decomposed by the 

addition of a sufficiently large quantity of a stronger acid, such as 

rochloric acid, when uric acid is set free : 

QK^a^A + 2HC1 = <yff *SA + 2XaCL 

If, :_ :iir ::lir: ~?.zi. :hi :■:_: :v:\: :: :- ::i r^ffrd o~ :n=u^::^:. :he 
acid salt is thrown down : 

CjH^a^ A HI" Ha = CjH^a^A + SaCL 
All these salts are difficultly soluble, and are, hence, precipitated 
whenever the urine is markedly acid or concentrated, and also when 
it is exposed to a low temperature. This holds good particularly for 
the acid salts, notably the ammonium compound. 

Uric acid that has separated out from the urine spontaneously may 
occur under a great variety of forms (Fig. 87), of which the so- 
called whetstone-form is the most characteristic (see Sediments). 








( 



(- 






i»c& - "'" - 



J, 




J 



When obtained from its alkaline solutions by the addition of hydro- 
chloric acid it usually forms small rhombic plates, which taper 
markedly toward their ends, being often club-shaped. 

Of the compounds which uric acid forms with the heavy metals, 
the silver salt is especially important. When a solution of uric 
acid in ammonia is treated with an ammoniacal solution of silver 
nitrate the solution remains clear. If, then, calcium chloride, sodium 



THE URINE. 317 

chloride, or magnesia mixture be added, a precipitate is formed which 
contains the uric acid in combination with the silver. 

Tests for Uric Acid. About 200 c.c. of filtered urine are treated 
with 10 c.c. of hydrochloric acid and set aside in a cool place for 
twenty-four to forty-eight hours. The uric acid which has separated 
out is then collected on a filter and subjected to further tests : 

1. Murexid test, A few crystals are dissolved by means of a few 
drops of concentrated nitric acid, with the application of heat, upon 
a porcelain plate, such as the cover of a crucible. The nitric acid is 
then carefully evaporated, when a yellowish-red spot will be found 
to remain. Upon cooling a drop of ammonia is placed upon this 
spot, when in the presence of uric acid a beautiful purplish-red color 
will develop, owing to the formation of ammonium purpurate (mur- 
exid). If now a drop of a sodium hydrate solution be added, the 
color will change to a reddish-blue, which disappears upon heating, 
thus differing from the somewhat similar xanthin reaction. 

2. Copper test. A few crystals are dissolved in sodium-hydrate 
solution and treated with a few drops of Fehling's solution. Upon 
the application of heat white urate of copper separates out, while red 
cuprous oxide appears if a relatively large amount of copper sulphate 
be present, a point to be remembered in testing for sugar. 

3. When treated with sodium hypobromite solution uric acid gives 
up about 47 per cent, of its nitrogen. 

Quantitative Estimation of Uric Acid. 

Haycraft's Method. This method is based upon the precipi- 
tation of uric acid with an ammoniacal silver solution and magnesia 
mixture, 1 molecule of silver corresponding to 1 molecule of uric 
acid. As the amount of silver thus precipitated cau be determined 
by titration with a solution of potassium sulpho-cyanide, the corre- 
sponding amount of uric acid is readily found. 

Solutions required : 1. An ammoniacal silver solution. 2. An 
ammoniacal maguesia mixture. 3. A one-fiftieth normal solution of 
nitrate of silver. 4. A one-fiftieth normal solution of potassium 
sulphocyanide. 

Preparation of these solutions : 

1. The ammoniacal silver solution is prepared by dissolving 26 
grammes of nitrate of silver in distilled water, adding enough am- 
monia to redissolve the brown precipitate of oxide of silver first 



318 CLINICAL DIAGNOSIS. 

formed ; distilled water is then added in sufficient amount to make 
the total quantity 950 c.c. This solution is brought to its proper 
strength by titrating a known amount of sodium chloride as described 
elsewhere. Each c.c. then contains 0.26 gramme of nitrate of silver, 
equivalent to 0.01617 gramme of silver. 

2. The ammouiacal magnesia mixture is prepared by dissolving 
100 grammes of crystallized magnesium chloride in a sufficient 
amount of water, to which a cold saturated solution of ammonium 
chloride is added in excess, and enough strong ammonia to impart 
a decided odor. Should the mixture not be perfectly clear, still more 
ammonium chloride solution is added. The solution is then diluted 
with water to 1 liter. 

3. The one-fiftieth normal solution of nitrate of silver is prepared 
by dissolving 3.4 grammes of silver nitrate in 950 c.c. of distilled 
water, the degree of farther dilution being determined as described 
elsewhere. 

4. To prepare the one-fiftieth normal solution of potassium sul- 
pho-cyanide, about 2 grammes of the salt are dissolved in 950 c.c. of 
water and the solution brought to the required strength, so that 1 
c.c. shall correspond to 1 c.c. of the silver solution. 

For filtering the uric acid a perforated platinum cone is placed in 
a small funnel and packed with a fine layer of glass-wool, upon which 
in turn a layer of finely scraped asbestos is arranged, this having 
been thoroughly washed out in very dilute hydrochloric acid and 
subsequently with distilled water until every trace of chlorine has 
disappeared, the asbestos forming, as it were, a mould of the cone. 

Method : Fifty c.c. of filtered urine are treated with 5 c.c. of the 
ammouiacal silver solution and 5 c.c. of the ammoniacal magnesia 
mixture. As soon as the precipitate has settled down somewhat, the 
supernatant liquid is filtered through the filter prepared as described, 
with the aid of a suction-pump. About 4 grammes of sodium bicar- 
bonate in coarse pieces are now placed upon the filter and the pre- 
cipitate added, the sodium bicarbonate serving the purpose of aiding 
filtration by loosening the precipitate. This is now washed free 
from chlorine and silver by means of ammouiacal water, using the 
suction-pump, until the precipitate appears broken in places, then 
without the pump, using this only at last to remove the last drops 
of liquid. For silver, test with very dilute hydrochloric acid, and 
for chlorine with a solution of nitrate of silver and nitric acid. The 
precipitate thus obtained is dissolved on the filter by means of 20 to 



THE URINR 3!9 

30 per cent, nitric acid. The nitric acid must be free from nitrous 
acid. This is accomplished by allowing it to stand in contact with 
pure urea until all evolution of gas lias ceased. The filter is washed 
with very dilute nitric acid and then with distilled water, until this 
no longer shows an acid reaction. The solution thus obtained is 
titrated with the one-fiftieth solution of potassium sulpho-cvanide, 
using ammonio-ferric alum as an indicator. As every e.c of this 
solution indicates 0.01617 gramme of silver, and as 1 molecule of 
silver indicates 1 molecule of uric acid — i.e., 108 grammes of silver 
168 grammes of uric acid — 0.01617 gramme of silver, corresponding 
to 1 c.c. of the potassium sulpho-cyanide solution, represents 0.0251 
gramme of uric acid. 

Ludwig-Salkowski method. This method should be employed 
whenever special accuracy is required. 

Principle : A solution of uric acid in sodium carbonate when 
treated with a solution of nitrate of silver, after a previous addition 
of an excess of ammonia, gives rise to a flaky, gelatinous precipitate 
containing uric acid, sodium, and silver, which is very difficultly sol- 
uble. From this the silver may be removed, and the compound of 
uric acid and sodium decomposed by means of hydrochloric acid. 

Method : Two hundred and fifty c.c. of urine are treated with 50 
c.c. of an ammoniacal magnesia mixture (see above) for the purpose 
of removing the phosphates. The magnesia mixture is employed 
for the reason that the compound of uric acid with magnesium and 
silver formed later on is not decomposed as easily as the sodium or 
the potassium compound, which would occur if the urine were only 
precipitated with ammonia. The mixture is then immediately filtered, 
as otherwise a little magnesium urate would be precipitated ; 250 
c.c. of the filtrate, corresponding to 200 c.c. of urine, are measured 
off as soon as possible and treated with a few c.c. of a 3 per cent, 
solution of nitrate of silver. If the precipitated silver chloride 
formed in the beginning does not disappear on stirring, a little more 
ammonium hydrate is added. A flaky precipitate falls next, which 
is allowed to settle. In order to test whether enough of the silver 
nitrate solution has been added, a few c.c. of the supernatant fluid 
are acidified with nitric acid. If a distinct cloudiness appears, refer- 
able to silver chloride, enough has been added. Otherwise the few 
c.c. that were employed fortius test are rendered alkaline again with 
ammonia, poured back, and more silver solution added until the 
required amount has been reached. The liquid is then rapidly filtered 



320 CLINICAL DIAGNOSIS. 

through a folded filter of rather loose paper, a feather or rubber- 
tipped glass rod being used for the purpose of removing all the pre- 
cipitate from the beaker. The precipitate is washed until a specimen 
of the washiugs is no longer rendered turbid by nitric acid, and only 
faintly so by the addition of a drop of silver solution . The filter 
with the precipitate is next placed in a wide-mouthed flask contain- 
ing about 200 c.c. of distilled water, and the mixture thoroughly 
shaken. Sulphuretted hydrogen is then passed though the mixture, 
which is thoroughly shaken from time to time. It is then brought 
to the boiling-point and rendered distinctly acid by means of a few 
drops of hydrochloric acid, when the sulphide of silver and the paper 
are rapidly filtered off, as otherwise there will be an admixture of 
sulphur with the uric acid. The contents of the filter are washed 
a few times with hot water. Filtrate and washings are quickly 
evaporated to a few c.c, to which a few drops of hydrochloric acid 
are added, and then set aside in a cool place for twenty-four hours. 
Occasionally it happens that upon the addition of the hydrochloric 
acid a cloudiness appears, due to an admixture of sulphur. In such 
a case the dried uric acid must be washed with carbon disulphide. 
Otherwise the uric acid that has separated out is directly collected on 
a dried and weighed filter and washed successively with water, 90 to 
94 per cent, alcohol, and finally with absolute alcohol and ether. 
The water used in washing should be collected separately, and 0.0048 
gramme added to the weight of the uric acid obtained for every 10 
c.c. used. 

Precautions : 1. Rapidity in workiug is most essential. 

2. Very concentrated urines must be diluted one-half before com- 
mencing the test. 

3. If the specific gravity of the urine be low, it should be concen- 
trated to a specific gravity of about 1.020. 

4. If the urine contain a sediment of uric acid, this should be 
separately collected and weighed, and the weight obtained added to 
the final result. 

5. Any albumin present should be previously removed. 

6. If sugar be present in the urine, about 500 to 1000 c.c. are 
treated with a solution of neutral acetate of lead, filtered, and the 
filtrate precipitated with mercuric acetate. The precipitate thus 
formed, which consists essentially of mercuric urate, is filtered off 
after having stood for twelve to twenty-four hours, first washed with 
and later suspended in water. The mercury is removed by means 



THE URINE. 321 

of sulphuretted hydrogen, the sulphide of mercury filtered off, and 
the filtrate collected and set aside. The precipitate Itself is thor- 
oughly boiled with water and again filtered, the washings thus ob- 
tained being added to the filtrate set aside, as just described. The 
total amount of fluid is then evaporated to a small volume and acid- 
ified with hydrochloric acid, when the uric acid will separate out and 
may be treated as set forth above. 

The old method of Heintz. The following method, although inac- 
curate, may be employed where the necessary solutions required for 
more accurate working are not at hanel: 

Principle : The urates contained in the urine are decomposed by 
means of hydrochloric acid, the uric acid formed being set free. 

Method : Two hundred c.c. of urine are treated with 10 c.c. of 
strong hydrochloric acid and set aside in a cool place for forty-eight 
hours. The crystals of uric acid which have been deposited by that 
time are collected on a small filter that has been dried at a tempera- 




Watch-crystals. (W. Simon.) 

ture of 110° to 115° C, and carefully weighed, using a cut-feather 
or a rubber-tipped glass rod to remove all the crystals from the 
bottom and sides of the vessel, portions of the filtrate being used to 
bring the last traces upon the filter. The crystals are then washed 
with cold water, care being taken to collect the washings separately, 
until a specimen no longer becomes cloudy when treated with a few 
drops of nitrate of silver and nitric acid. Funnel and filter are then 
dried in the hot-air bath at a temperature of 110° to 115° C, and 
the filter finally dried to a constant weight at the same temperature. 
The filter is most conveniently dried between watch-glasses (Fig. 88), 
two of these being employed, one placed inside the other during the 
process of drying, while one is covered by the other and held in posi- 
tion by a spring during the process of weighing. The weight of the 
glasses and clamp, as well as that of the filter, is deducted from the 
total weight, the difference indicating the weight of the uric acid 
contained in 200 c.c. of urine. As the uric acid, however, is slightly 

21 



322 CLINICAL DIAGNOSIS. 

soluble in acidified urine and acidified water, a loss will always arise, 
if this method be employed. If but 30 c.c. of water are used during 
the process of washing, however, the loss will practically be coun- 
terbalanced by the weight of the coloring-matter which is carried 
down by the crystals. It has been estimated, furthermore, that for 
every 10 c.c. of water used beyond the amount indicated the addi- 
tion of 0.0045 gramme to the weight obtained will make up for the 
loss of uric acid thus resulting. 

While this method may be employed for clinical purposes, as a 
rule, it must be remembered that at times only a portion of the uric 
acid, or none at all, separates out. Its absence should not, however, 
be inferred under such conditions, as its presence may be demonstrated 
by alkalinizing the acid filtrate and treating this with a solution of 
nitrate of silver, when a considerable precipitation may occur refer- 
able to the presence of uric acid. A test such as this should always 
be made, and if a considerable cloudiness be obtained, recourse should 
be had to one of the methods indicated above. 

In addition to the precautions given the following should be noted: 
1. Urines rich in uric acid should be warmed after the addition of 
the hydrochloric acid until the cloudiness which occurs upon the 
addition of the reagent owing to the presence of acid urates has disap- 
peared. If a sediment or cloudiness, due to urates, be noted in the 
urine, it should be warmed, and if necessary a small amount of alkali 
added, before the addition of the hydrochloric acid. 

Hippuric Acid. 

Hippuric acid is a constant constituent of normal urine, 0.1 to 1 
gramme being excreted in the twenty-four hours. That it is derived 
to some extent at least from albuminous material is proved by the 
fact that its elimination is not suspended during starvation, or during 
the administration of a purely albuminous diet. The manner in 
which hippuric acid is formed in the body-economy, however, has not 
been definitely ascertained. In vitro it may be obtained from glyco- 
coll and benzoic acid, according to the equation : 

C 6 H 5 -f CH 2 NH 2 = CH 2 XH— C 6 H 5 CO + H 2 

COOH COOH COOH 

Benzoic acid. Glycocoll. Hippuric acid. 

It has been shown that phenyl-propionic acid, which differs from 
benzoic acid by the group C 2 H 4 , and which latter may be regarded 



77//; URINE, ;>2;; 

as phenyl-formic acid, is produced during the process ol intestinal 

putrefaction, the relation between the two bodies being seen from the 
formula? : 





CH 3 <H.-C 6 H 5 


h cyi 5 


1 1 


1 — >■ 1 


CH a — y CH 2 


COOH COOH 


1 | 




COOH COOH 


Formic Phenyl-formic 


Propionic Phenyl-propionic 


acid. acid. 


acid. acid. 



Phenyl-propionic acid is then absorbed into the blood and there, 
according to our present ideas, transformed into phenyl-formic acid, 
or benzoic acid. The latter coming into contact with glycocoll, which 
is probably produced during the process of intestinal putrefaction 
also, an interaction between the two substances occurs, hippuric acid 
resulting, as shown in the above equation. This view is supported 
by the fact that phenyl-propionic acid, just as benzoic acid, when 
introduced into the circulation of certain animals, reappears in the 
urine as hippuric acid. The final proof of the possible synthesis of 
hippuric acid from glycocoll and benzoic acid in the body has been 
furnished by Bunge and Schmiedeberg, who obtained this substance 
when arterialized blood containing glycocoll and sodium benzoate 
was allowed to pass through isolated kidneys of dogs. 

Not all the hippuric acid eliminated, however, is referable to albu- 
minous material, but a considerable portion is derived from the ben- 
zoic acid, or its derivatives, which latter, contained in many of the 
fruits eaten as food, are transformed into hippuric acid in the body. 
Among those which are particularly rich in these substances there 
must be mentioned the red bilberry, prunes, coffee-beans, reines- 
claudes, etc., and in all cases in which an increased elimination of 
hippuric acid is observed the possibility of this source must always 
be taken into account. 

As to the seat of this synthesis there appears to be some uncer- 
tainty, it not appearing to be the same in all animals. In the dog 
and frog the kidneys, according to the researches of Bunge and 
Schmiedeberg, must be regarded as the principal and possibly the 
only organs in which this process occurs. As Salomon, however, 
has demonstrated the presence of hippuric acid in the muscles, liver, 
and blood of nephrectomized rabbits, there must be, in the herbivora 
at least, other organs concerned in its production. 

Very little is known of the pathologic variations in the excre- 
tion of hippuric acid, principally owing to the fact that suitable 



324 



CLINICAL DIAGNOSIS. 



methods for its quantitative estimation were unknown until recently. 
It is an interesting fact that, in accordance with Bunge's experi- 
ments in dogs, the elimination of hippuric acid appears to be entirely 
suspended in cases of acute as well as chronic parenchymatous 
nephritis, following the ingestion of benzoic acid, this reappearing 
unchanged in the urine. In amyloid degeneration a marked diminu- 
tion in its amount has likewise been demonstrated. Large quantities 
of hippuric acid, on the other hand, have been noted in acute febrile 
diseases, hepatic diseases, diabetes mellitus, chorea, etc. The data, 
however, are insufficient to warrant any definite conclusions at the 
present time. 

Properties of Hippuric Acid. Chemically, hippuric acid must 
be regarded as benzoyl-amido-acetic acid, C 9 H 9 N0 3 (C 6 H 5 .CONH. 



Fig 




CH 2 COOH). It crystallizes in long rhombic prisms when allowed 
to separate from it solutions gradually, while it forms long needles 
if crystallization takes place rapidly and the amount is small (Fig. 
89). In water and ether it is soluble with difficulty, while it dis- 
solves readily in alcohol and in aqueous solutions of the hydrates 
and carbonates of the alkalies, forming -salts, from which the acid 
may again be separated and caused to crystallize out upon the addi- 
tion of a stronger acid. 

When hippuric acid or one of its salts is evaporated to dryness 
with concentrated nitric acid and the residue heated the odor of 
bitter almonds is noticed, due to the formation of nitro-benzol. 

When boiled with hydrochloric acid or dilute sulphuric acid it is 



THE URINE. 325 

decomposed into glycocoll and benzoic acid. A similar decomposi- 
tion is effected during the process of putrefaction, and hence do 
hippuric acid is found in decomposing urine, benzoic acid taking its 

place. The latter is always found in the urine together with hippuric 
acid, but has no clinical significance. It crystallizes in lustrous 
laminae or needles, the former presenting ragged edges and resem- 
bling' somewhat plates of cholesterin. It is difficultly soluble in cold 

water, but easily soluble in ether, alcohol, and solutions of the alka- 
line carbonates and hydrates, forming salts with the latter. 

Hippuric acid in the urine occurs in combination with sodium, 
potassium, calcium, and magnesium. 

Quantitative Estimation of Hippuric Acid. The following 
method, which may be employed for the quantitative estimation of 
hippuric acid, although very tedious, must also be employed when it 
is desired to test for its presence. 

Principle : Hippuric acid readily dissolves in solutions of the 
alkaline hydrates and carbonates, forming salts. These are decom- 
posed by means of a stronger acid, when the hippuric acid which 
separates out is collected and weighed. ■ 

Method : Five hundred to one thousand c.c. of fresh urine are 
evaporated to a syrupy consistence on a water-bath, care being taken 
to keep the urine neutral by the addition of sodium carbonate from 
time to time. The residue is extracted with cold alcohol (90 to 95 
per cent.), taking about half of the quantity as that of urine employed, 
and setting aside the mixture for twenty-four hours. The alcoholic 
filtrate, which contains the salts of hippuric acid, is then freed from 
alconol by distillation. The remaining solution is strongly acidified 
with acetic acid, in order to liberate the lactic acid, and extracted 
with at least five times its own volume of alcoholic ether (1 part of 
alcohol to 9 parts of ether). From the combined extracts the ether is 
distilled off and the remaining solution evaporated on a water-bath. 
The resinous residue is boiled with water, set aside to cool, and 
filtered though a well-moistened filter. The hippuric acid, which is 
easily soluble in boiling water, is thus separated from other constit- 
uents soluble in alcohol and ether. The filtrate is rendered alkaline 
with a little milk of lime, any excess of calcium hydrate being re- 
moved by passing carbon dioxide through the mixture. This is then 
brought to the boiling-point and filtered. Any impurities present 
are removed by shaking with ether. The calcium salts remaining 
in solution are decomposed by means of an acid and the solution 



326 CLINICAL DIAGNOSIS. 

again extracted with ether. The remaining solution is evaporated 
to a few c.c., when the hippuric acid will separate out on standing. 
The crystals are dried on plates of plaster-of-Paris, shaken with 
benzol or petroleum-ether to remove any benzoic acid, and finally 
weighed. These crystals may be shown to be hippuric acid by their 
microscopic appearance, their solubility in alcohol, and their be- 
havior when evaporated with concentrated nitric acid as indicated 
above. 

Hofmeister's method : Two hundred to three hundred c.c. of urine 
are evaporated in a glass dish to one-third of the original volume, 
treated with 4 grammes of disodium phosphate to transform the 
acid into its sodium salt, and the mixture evaporated to a syrupy 
consistence. The residue is treated with burnt gypsum, dried thor- 
oughly, and pulverized together with the dish. The powder is ex- 
tracted in a Soxhlet apparatus with freshly rectified petroleum-ether 
(boiling-point 60° to 80° C.) for forty-six hours, and then for six to 
ten hours with pure ether (free from water and alcohol). After 
distilling off the ether, the residue is dissolved in boiling water, and 
decolorized with animal charcoal, the latter being subsequently thor- 
oughly washed with boiling water ; the solution and washings are 
evaporated to about 1 to 2 c.c. at a temperature of from 50° to 60° C, 
and set aside to crystallize. The crystals of hippuric acid are finally 
washed with a few drops of water and ether, and weighed. 

Kreatin and Kreatinin. 

Numerous observations point to kreatin, which is constantly present 
in muscle-tissue, as being in all probability the immediate and con- 
stant antecedent of kreatinin, so that two sources of this body must 
be recognized, viz., the muscle-tissue of the body and the muscle- 
tissue ingested as food. Beyond this, however, practically nothing 
is known, and as the artificial production of kreatinin from albu- 
minous material has so far never been accomplished, it is hardly 
warrantable to venture an hypothesis as to its mode of formation in 
the body. 

Kreatinin is a constant constituent of the urine, about 1 gramme 
being daily excreted by a healthy adult. Pathologically variations 
in this amount have been observed, but the data so far obtained pos- 
sess little value, and before drawing any conclusions from facts chem- 
ically observed it is necessary to take into account the quantity of 
meat ingested by the individual, as a meat-diet will increase the 



THE URINE, 327 

amount of kreatinin, while this will be diminished by a milk-diet. IV 
then in patients affected with acute febrile diseases, such as pneumonia, 

typhoid fever, etc., a large increase is observed, the patient being at 
the same time upon a milk-diet, an increased destruction of muscle- 
tissue may be inferred. A decrease would logically be expected to 
occur during convalescence from such diseases. In the various forms 
of anaemia, marasmus, chlorosis, phthisis, etc., a diminished amount 
is observed. 

The transformation of kreatin into kreatinin has been supposed to 
take place in the kidneys, a view which accords with the greatly 
diminished excretion of kreatinin in well-advanced cases of chronic 
parenchymatous nephritis. In progressive muscular atrophy, in 
pseudo-hypertrophic paralysis, and in progressive ossifying myositis 
a diminution has been noted. 

Properties of Kreatin and Kreatinin. Chemically kreatin 
may be regarded as a methyl derivative of glycocyanin, which latter 
is guanidin in which one NH 2 group has been replaced by glycocoll. 
Kreatinin, on the other hand, is the methyl derivative of glycocy- 
anidin, which differs from glycocyanin only in the absence of 1 mole- 
cule of water, so that kreatinin is kreatin minus 1 molecule of 
water, both being derivatives of guanidin. The relation between 
these various bodies is seen below : 

/NH 2 

C=NH 

\NH 2 
Guanidin. 

/XH 9 /NH 2 

C=XH" C=NH 

\XH.CH 2 .COOH \N(CH 3 ).CH 2 .COOH 

Glycocyanin. Kreatin. 

/NH /NH 

C=NH C=NH 

\NH.CH 2 .CO \N(CH 3 ).CH 2 .CO 

Glycocyanidin (glycocyanin minus water). Kreatinin (kreatin minus -water). 

Kreatinin crystallizes without water of crystallization in colorless, 
glistening prisms. At times when the crystals are not well devel- 
oped, it also appears in the form of whetstones. It is readily sol- 
uble in hot and also quite soluble in cold water and hot alcohol, but 
more difficultly so in cold alcohol and ether. 

It forms salts with acids and double salts with some of the salts 
of the heavy metals. Among these may be mentioned kreatinin 
hydrochloride, C 4 H 7 N 3 0.HC1, which is easily soluble in water and 



328 



CLINICAL DIAGNOSIS 



crystallizes in the form of transparent prisms or rhombic plates. 
Most important is the compound of kreatinin with zinc chloride, 
(C 4 H 7 N 3 0) 2 .ZnCl 2 (Fig. 90). This is produced when a watery or 
alcoholic solution of kreatinin is treated with chloride of zinc. The 
crystalline form of this compound depends greatly upon the purity 
of the kreatinin solution. When obtained from alcoholic extracts of 
the urine it occurs in the form of varicose couglomerations which 
often adhere firmly to the walls of the vessel. If the solution of 
kreatinin be perfectly pure, however, it is seen in the form of fine 
needles grouped together in rosettes or sheaves. Kreatinin-zinc 
chloride is very difficultly soluble in water and insoluble" jn alcohol. 



Fig. 90. 




Crystals of kreatinin-zinc chloride. (Salkowski.) 

This compound is especially important, as upon its formation and 
properties the quantitative estimation of kreatinin in the urine is 
based. Nitrate of silver and mercuric chloride cause a precipitation 
of kreatinin, and may, therefore, also be employed for the purpose 
of obtaining the substance from the urine. 

Test for Kreatinin in the Urine. A few c.c. of urine are 
treated with a few drops of a very dilute solution of sodium nitro- 
prusside and then drop by drop with a dilute solution of sodium 
hydrate, when the urine in the presence of kreatinin assumes a ruby- 
red color, which is particularly well visible in the lowest portion of 
the tube. This color disappears after a few minutes, and is replaced by 
an intensely yellow color which on warming with glacial acetic acid 
in pure solutions gives rise to a green color ( Weyl's test). The pres- 
ence of albumin or sugar does not interfere with the reaction. 



THE URINE. 329 

Quantitative Estimation of Kreatinin in the Urine. Prin- 
ciple : When an alcoholic extract oi the urine is treated with an 
alcoholic solution of zinc chloride 1 kreatinin-zinc chloride separates 
out, which, as has been mentioned, is almosl insoluble in alcohol. 

Knowing the molecular weight of kreatinin and kreatinin-zinc chlo- 
ride, the calculation of the amount of kreatinin becomes a simple 
matter. The molecular weight of kreatinin is 113, thai of krea- 
tinin-zinc chloride 362. In 362 parts by weight of the latter there 
are, hence, 226 parts by weight of the former, so that the amount of 
the kreatinin may be calculated from the weight of kreatinin-zinc 
chloride according to the following equation : 362 : 226 : : y : x, and 
x = 0.6243y, in which y indicates the weight of the kreatinin-zinc 
chloride found, and x the corresponding amount of kreatinin. The 
phosphates must, of course, first be eliminated, as insoluble zinc 
phosphate would otherwise be precipitated. 

Method : In 240 c.c. of urine the phosphates are first removed by 
rendering the urine alkaline with milk of lime and then adding cal- 
cium chloride as long as a precipitate forms. If the volume now 
be less than 300 c.c, water is added to that amount. The mixture 
is filtered after having been allowed to stand for one-quarter to one- 
half an hour, and washed with a little water ; 250 c.c. of the mix- 
ture are then measured off, slightly acidified with dilute hydrochloric 
acid so as to prevent any transformation of kreatinin into kreatin 
during the long process of evaporation. This amount is evaporated 
on a water-bath to a syrupy consistence, and then thoroughly 
mixed with 20 to 30 c.c. of absolute alcohol. The mixture is 
poured into a stoppered flask provided with a 100 c.c. mark, and 
after thoroughly rinsing out the evapo rating-dish with absolute alco- 
hol the washings are also placed in the bottle and absolute alcohol 
added to the 100 c.c. mark. The bottle is thoroughly shaken and 
set aside in a cool place for twenty-four hours, the mixture being 
agitated from time to time. It is now filtered and rendered slightly 
alkaline with a drop or two of sodium carbonate solution, as krea- 
tinin hydrochloride is not precipitated by chloride of zinc. The 
reaction, however, should be only faintly alkaline, as otherwise zinc 
oxide will be precipitated. The mixture is now slightly acidified 
with acetic acid. Eighty c.c, corresponding to 160 c.c. of urine, 
are treated with 10 to 15 drops of an alcoholic solution of zinc chlo- 
ride, prepared by dissolving the salt in 80 per cent, alcohol and dilut- 
ing with 95 per cent, alcohol to a specific gravity of 1.2. The 



3 3fl 7L TNIOAL DIAGNOSIS. 

mixture is then well stirred and set aside in a cool place for two or 
three lays. T he crystals, which are usually deposited upon the sides 
of the vessel in the form of wart-like masses, are then collected upon 
a dried and weighed filter, always using portions of the filtrate to 
bring the crystals completely upon the filter. These are washed 
with a small amount of 90 per cent alcohol until the washings are 
without color and give only a slight opalescence when treated with 
a drop of nitrate of .silver solution. The crystals are finally dried 
at a temperature of 100° C, and weighed. By multiplying the 
weight thus found by 0.6243 the amount of kreatinin is obtained. 

Precautions : 1. Albumin and sugar, if present, must first be 
removed. In diabetic urines it is best, after having removed the 
6 g i fermentation, to take one-fifth of the total quantity eliminated 
in twenty-four hours, and to evaporate this to about 300 c.c before 
removing the phosphates. 

2. Tur weighed material should be examined microscopically to 
see whether notable quantities of sodium chloride be present. Should 
such be the case it is necessary to determine the amount of zinc pres- 
ent and to estimate the kreatinin from this. To this end the alco- 
holic solution containing the kreatinin-zinc chloride is evaporated to 
dryness after the addition of a little nitric acid. The residue is in- 
oin-rr:;:^!. tx::-::t^ with water, washed, dried, fused, and finally 
weighed. 

As 100 parts of kreatinin-zinc chloride correspond to 22.4 parts 
weight of zin: le corresponding amount of the compound 

is round according to the following equation : 22.4 : 100: :y : x. 
and x =4.4642. in which y represents the amount of zinc oxide 
found, and x the corresponding amount of kreatinin-zinc chloride. 
By multiplying the number thus ascertained by 0.6243 the corre- 
ling amount of kreatinin is found. 

3. I n -Trad of doing this the precipitate in the alcoholic solution 
may be examined ; topically before filtering, and if sodium 
chloride srystals be found, providing that the kreatinin-zinc chloride 

-:ils adhere to the sides of the vessel, the sodium chloride may 
e dissolved in a litr and poured off. 

4. If the aystals of kreatinin-zinc chloride adhere very firmly to 
the sides of the vessel, so that their removal would be incomplete, it 

rrhaps best to dissolve them in a little hot water, to evaporate 
■-.'"-■• - • ■ ^h the kreatinin compound directly. 

5. It the urine shows an alkaline reaction, it is best to acidify 



THE U III Si:. 331 

with sulphuric acid and to boil for hair an hour, before removing the 
phosphates, so as to transform any fereatin that may be present into 
kreatinin, when the examination should be continued as described. 

The Xanthin Bases. 

The xanthin bases which have been found in the urine are : Xan- 
thin, heteroxanthin, paraxanthin, hypoxanthin, guanin, adenin, and 
carnin. The relation existing between these bodies is seen from their 
formulae : 



Hypoxanthin 

Xanthin 

Heteroxanthin 

Paraxanthin 

Adenin 

Guanin 

Carnin 



W 4 o 

C 5 H,N 4 2 
C 5 H 8 (CH 8 )N 4 O a 

C 5 H 2 (CH :{ UXA 
C 6 H B N 6 



• • • C 7 H 8 N 4 3 
The quantity of these bodies present in the urine is so small that 
uuless characteristic reactions, directly applicable to the urine, are 
discovered, by means of which an approximate idea may be formed 
of the quantity in a given specimen, it is very unlikely that the vari- 
ations in the amount of these substances excreted will ever become 
of practical importance. To give an idea of the very small amount 
in which these substances occur in the urine, it will be sufficient to 
state that Xeubauer was able to obtain but 1 gramme of xanthin 
from 300 liters of urine. 

Hypoxanthin appears to be a derivative of nuclein, as large quan- 
tities of the former substance result from the decomposition of the 
latter when treated with mineral acids. With this observation the 
fact that an increased elimination of hypoxanthin is noted in cases 
of splenic leukaemia is in perfect accord. In general, however, the 
mode of origin of these bodies is unknown and the small number 
of observations made upon their excretion not sufficient to warrant 
definite conclusions. 

Clinically the xanthin bases possess a certain degree of interest 
from the very rare occurrence of sediments and calculi consisting of 
almost pure xanthin. The reactions, by means of which the xanthin 
bases maybe recognized, will be described under Sediments. 

Oxalic Acid. 

The origin of oxalic acid in normal urine appears to be twofold, 
one portion being referable to vegetable food ingested, the other orig- 



332 CLINICAL DIAGNOSIS. 

mating in the body in a manner not definitely understood at the 
present time. It is quite probable, however, that this latter portion 
is derived, to some extent at least, from uric acid through a process of 
oxidation, a view which is supported by the artificial production of 
oxaluric acid from uric acid, the former being likewise a constant 
constituent of the urine ; oxaluric acid is readily decomposed into 
oxalic acid and urea, as is seen from the following equations : 



2. 



C 5 H 4 N 4 3 + + H 2 = C 4 H 2 N 2 4 + CON 2 H 4 
Uric acid. Alloxan. Urea. 


C 4 H 2 XA + o = 

Alloxan. 


/NH.CO 

-- CO | + C0 2 . 
\NH.CO 

Parabanic acid. 


/NH.CO CO— XH- CONH 2 . 
CO | + H 9 = | 
\NH.CO CO.OH 


Parabanic acid. 


Oxaluric acid. 


CO— NH— CONH 2 CO— OH /NH 2 . 
| + H,0 = I + CO 
CO.OH CO-OH \NH 2 . 


Oxaluric acid. 


Oxalic acid. Urea. 



Oxalic acid may also result from an insufficient oxidation of car- 
bohydrates. 

From a pathologic standpoint the study of the excretion of oxalic 
acid is of decided importance. Care should, however, be taken in 
the interpretation of the results reached by a chemical examination, 
as numerous vegetable substances are capable of producing an exces- 
sive excretion of this acid. Among these may be mentioned toma- 
toes, spinach, carrots, celery, string beans, asparagus, apples, grapes, 
etc. 

Gastro-intestinal disturbances are very apt to cause an increased 
elimination of oxalic acid, probably in consequence of a defective 
digestion and subsequent oxidation of carbohydrates, the so-called 
nervous oxaluria being probably of this origin. Very interesting is 
the form of oxaluria observed in cases of transient albuminuria, 
described by Senator, and confirmed by v. Noorden and others. To 
this class the so-called Albuminuria and BrigMs Disease of Uric 
Acid and of Oxalic Acid of Da Costa in all probability also belongs. 

In the chapter on Phosphates it was shown that a certain relation 
appears to exist at times in diabetes mellitus between the excretion 
of sugar and phosphates, these bodies increasing and decreasing 
in an inverse relation to each other. A similar condition is also 
noted in the excretion of uric acid. In the case of oxalic acid such 



the urn si:. 333 

a vicarious elimination, as it were, is likewise not infrequently 
observed and may at times be very pronounced, indicating the exist- 
ence of a probable relation between carbohydrates and oxalic acid. 

The oxalic acid diathesis, or idiopathic oxaluria, must finally be 
considered. In this condition there is associated with a definitely 
recognizable increased production a temporary retention, followed bv 
an increased elimination of oxalic acid, notwithstanding the fact that 
a perfectly normal diet — i. e., one not especially rich in oxalic-acid- 
containiug constituents — may be taken. There can thus be no doubt 
of the occurrence of abnormal metabolic processes in the body. These 
are probably similar to those giving rise to diabetes mellitus, there 
being, as it were, a suspended oxidation in diabetes and an insuf- 
ficient oxidation in the idiopathic oxaluria, the relation between 
the two diseases being further shown by the vicarious elimination 
of oxalic acid iu diabetes. 

Clinically two forms of this disease have been described, one char- 
acterized by a progressive loss of flesh, occurring in already emaci- 
ated subjects, general malaise, various dyspeptic and neurasthenic 
symptoms, pain in the lumbar region, etc. In the other form the 
subjects are usually fat, and furunculosis, neuralgic or lancinating 
pains, neurasthenic symptoms, etc., are present. The possible, and, 
indeed, very probable, formation of renal or vesical calculi, if the 
disease be neglected, should also be remembered. 

Properties of Oxalic Acid. Oxalic acid occurs in the urine as 
calcium oxalate, CaC 2 4 , being held in solution by the diacid sodium 

Fig. 91. 




Calcium oxalate crystals. 



phosphate. It can, hence, be thrown down by diminishing the acid- 
ity of the urine by the addition of a little ammonia, for example, or 
by allowing it to stand exposed to the air. Calcium oxalate, when 



- ; _ ;:2~;±: dla -:\ ;: 

allowed to crystalline oat slowly, occurs In the form, of well-defined, 
^Fongiy lefEarfive octahedra, the well-known envelope-forms re- 
3 - ing, in which the principal axis of the crystals is placed at right- 

__'.-- - :!if plane of the microscopic slide T._ 1 
Calcium oxalate may always be recognized by its characteristic 

. f ~als, its insolubilifcy in acetic acid, and its solubility in hydro- 
chloric add. When strongly heated it is decomposed into calcium 
oxide,, carbon dioxide, and carbon monoxide, according to the equa- 



\ == M - - OCX 

I„t ::::_:::" fz:: -.'.- :~ :_r : — ri: - -: : :: _ : 'i:s ~ir.^ h il hi". 
- « :■:• 2i milligrammes. Ir must be remembered here that an 
faksmeased or dmtmisked extreSkm of oroMc add etnmci be determined 
big a mieimse&pie examimatiem of the sediment, as wamerams eiys- 
iab of Gax&tiate of eahsmm way be seen when a quanititiHitre estiivia- 



Teste for Oxalic Acid. For the detection of calcium oxalate 
: - ; frequently only necessary to examine the sediment of the urine 
after twenty-four to forty-eight hours, but. as has been pointed out, 
n: :.-;..::•.- :"----..- zl:-.~ :e :::i. rri ~ IrZ i~ :■. : z :rn::— 7 - -:^- 
izi : .-_!-. :y chemical methods. In such cases it 

is usually possible to bring abont the crystallization of the salt by 

- it \- ::.\ :::,' the urine with a little ammonia. Shonld this 

_ : c lead to the desired result, it is best to proceed by a 
method which may at the same time be employed for the purpose of 
estimating the entire amount of oxalie acid. 

Qo&ntit&trve Estimation of Oxalic Acid. Principle : The 
oxalate of ealeium occurring in the urine is held in solution by the 
diacid sodium phosphate. If this be removed by means of calcium 
chloride- and ammonia, the calcium :z :. ':.:- is ;^eipitated. By heat- 

r ~ - - " igly - ■ on - : : med into calcium oxide. 

--- r . ; :. ::s -__::: calcium oxide correspond to 128 parts 

by weight of calcium oxalate, the amount of the latter can be readily 
calculated according to the equation : 06 : 128 : : y : x, and x = 
- _ ] ' f . in which y indicates the amount of calcium oxide f ouiid in 
a given amount of mine, and x the corresponding amount of calcium 
oxal a te ., As 1 moJeeoJe of oxalic acid, moreover, corresponds to 1 
mo leen le of calrinm oxalate, the amount of the former can be found 
:::- '-'a: : : hzzez •: o:-Lz_- z: :_, r :::.:_ 1_- [•■: ~ z. 



THE URINE. 335 

and x = 0.703y, in which y represents the amount ol calcium oxa- 
late found, and x the amount of the corresponding acid. 

Method : A large amount or urine (600 to 1000 c.c), alter having 
been treated with a small amount of an alcoholic solution of thymol, 
so as to guard against putrefactive processes, is treated with calcium 
chloride and ammonia added in excess in order to remove the diacid 
sodium phosphate which holds the oxalic acid in solution. During 
this process the oxalate of calcium is thrown down together with the 
phosphates. The precipitate is then carefully treated with an amount 
of acetic acid just sufficient to dissolve it. As calcium oxalate is 
insoluble in acetic acid, it gradually separates out. To this end the 
mixture is allowed to stand for twenty-four hours, the addition of the 
thymol preventing the development of bacteria. At the end of this 
time the calcium oxalate is filtered off through a small filter. It is 
then washed with a small amount of water and dissolved with a few 
drops of hydrochloric acid, any uric acid that may have separated 
out being left behind. The filtrate is then treated with a small 
amount of very dilute ammonia, so as to render the solution slightly 
alkaline. After standing for twenty-four hours the calcium oxalate 
will have separated out, and is collected upon a small filter, the 
weight of the ash in this being known. After washing with water 
the contents of the filter are dried and incinerated in a crucible, heat- 
ing strongly for about twenty minutes, whereby the oxalate is trans- 
formed into the oxide. From the weight of this the corresponding 
amount of oxalic acid is readily calculated according to directions set 
forth above. 

Albumins. 

The albumins which may be met with in the urine are : Serum- 
albumin, serum-globulin, albumoses (peptones), haemoglobin, nucleo- 
albumin, fibrin, and histon. Of these, serum-albumin is the most im- 
portant from a clinical standpoint, and whenever in the following 
pages the term albuminuria is employed it should be remembered 
that serum-albuminuria is meant. 

Serum-albumin. The question whether or not serum-albumin 
occurs normally in the urine — i.e., under conditions strictly physio- 
logic in their nature — has been much disputed, it being claimed by 
some that, temporarily at least, traces may be met with in a large 
number of individuals, particularly after severe muscular exercise, 
cold baths, mental labor, severe emotions, during the process of men- 



336 CLINICAL DIAGNOSIS. 

struation, digestion, etc. This so-called physiologic albuminuria 
mostly occurs in young adults, aud is usually, if not always, of brief 
duration, the urine, it is claimed, being otherwise entirely normal ; 
i. e., of normal amount, appearance, specific gravity, and composition, 
and free from abnormal morphologic constituents, such as casts, red 
corpuscles, leucocytes, and epithelial cells. The persons examined 
must, furthermore, be entirely free from subjective or objective 
abnormalities. 

The existence of a physiologic albuminuria, on the other hand, is 
denied, and the occurrence of serum-albumin at least regarded as 
pathologic in every case. The author has never been able to convince 
himself of the presence of serum-albumin in the urine under condi- 
tions strictly physiologic, and it has already been pointed out else- 
where that severe muscular as well as mental labor, severe mental 
emotions, cold baths, etc. , can hardly be regarded as physiologic stim- 
uli for all persons. The albuminuria so often observed during the 
first days of life, at which time also sediments of uric acid and urates, 
mucus, epithelial cells from the different portions of the urinary tract, 
and even casts may be seen, constituents which in adults would rightly 
be regarded as abnormal, is also brought forward in support of the 
existence of a physiologic albuminuria. There can be no doubt, how- 
ever, that this form of albuminuria is referable to the profound changes 
which take place in the circulatory system after birth, and to some 
extent perhaps also to the well-known uric-acid infarctions so fre- 
quently seen in the kidneys of the newly born, so that it would 
probably be better and more in accord with the teachings of pathol- 
ogy to regard this albuminuria as abnormal. 

The more closely the subject of the so-called physiologic albumi- 
nuria is studied the more improbable does its physiologic nature 
appear, and a more detailed study of the metabolic processes, it may 
be confidently asserted, will ultimately lead to the conclusion that 
the presence of albumin in every case is a pathologic phenomenon. 

The association of an increased elimination of urea and uric acid 
with albuminuria in apparently healthy individuals was noted twenty- 
five years ago, but received comparatively little attention. More 
recently Da Costa, in a paper entitled " The Albuminuria and 
Bright's Disease of Uric Acid and Oxalic Acid," pointed out the 
existence of albuminuria associated with lithuria and oxaluria. 
Personal observations have led the author to look upon this form of 
albuminuria as being of common occurrence, and while in almost 



THE URINE. 337 

every case the albumin can be caused to disappear from the urine by 
proper diet and exercise, there can be qo doubt that if neglected 

granular atrophy may ultimately result. 

An albuminuria may at times be observed in anaemic children and 
adolescents, and particularly so in masturbating boys oi the mouth- 
breathing type, but can hardly be regarded as physiologic. The 
same may be said of the albuminuria of pregnancy and parturition. 

The course which these various forms of what should be termed 
functional albuminuria, in which the amount of albumin rarely exceeds 
0.1 per cent., may take, is very interesting. While the elimination 
of albumin may thus be quite transitory on the one hand, as when 
following severe muscular exercise, cold baths, and the like, it may, 
on the other hand, last for several days or even weeks, to be fol- 
lowed by a disappearance of the albumin for a variable length of 
time, and again by its reappearance and continuance for days and 
weeks. To this latter type the term intermittent albuminuria has 
been applied. At times the albuminuria may follow a definite course, 
disappearing and reappearing with such a degree of regularity that 
this form has not improperly been styled cyclic albuminuria. The 
albumin here generally disappears from the urine during the night, 
or at least during a prolonged period of rest in bed, to reappear 
again during the day, the erect posture apparently favoring its 
reappearance, so that the term postural albuminuria has also been 
suggested for this form. Osswald, who made a careful study of 
cyclic albuminuria in Riegel's clinic, regards its occurrence as dis- 
tinctly pathologic, and as indicating the existence of nephritis. 
Remembering the importance of the subject, it may not be out of 
place to enumerate the reasons which led Osswald to this conclusion : 

1. The patients generally come to the physician complaining of 
certain definite symptoms which are the same as those noted in cases 
of true nephritis. At times, however, no complaints are made, 
because the patients have reasons for concealing these (as in exam- 
inations for life insurance), or because they are for the time being 
absent. 

2. The subjective complaints, as well as the anemia so frequently 
observed in such cases, generally disappear, together with the albu- 
min, under suitable treatment, to reappear when the anaemia again 
becomes marked. 

3. In many a history of an antecedent nephritis, the result of 
scarlatina or diphtheria, may be obtained, as in three cases of Heub- 

22 



338 CLINICAL DIAGNOSIS. 

ner. in f c ases our of twenty described by Johnson, etc. In 

some also a direct transition from an acute nephritis to the cyclic 
form of albuminuria has been noted. Where this was not possible 
the history of an acute infectious disease or an angina, that had been 
overlooked in the clinical history, must be regarded as a possible 
cause. 

-A. The absence of morphologic elements, especially tube-casts, 
does Dot negative a nephritis. A large number of cases, however, 
have recently been observed in which casts were repeatedly found. 

5. A cyclic albuminuria may be observed in many cases of chronic 
nephritis. 

6. Marked organic abnormalities such as heart-lesions) need not 
be demonstrable, as they may be absent for a long period of time, or 
may be unrecognizable. 

Senator's statement that the existence of a physiologic albumi- 
nuria is proved by the fact that the morphologic constituents of 
the primitive nubecula contain albumin requires no further criticism, 
and should be regarded as a misconstruction of the main point at 
issue, a mere sophism, and Posner's observations, in view of the 
researches of Malfatti, which tend to show that the body obtained 
bv Posner was not serurn-aibumin, but a nucleo-albumin, may now 
be regarded as erroneous. 

In conclusion, it may safely be said that a transitory, intermittent, 
and cyclic albuminuria is not infrequently observed in apparently 
healthy individuals, but that the facts so far brought forward do not 
warrant the assumption that such forms of albuminuria are physiologic. 

It would lead too far to enter into a detailed consideration of the 
various causes that have from time to time been suggested as an ex- 
planation of the fact that albumin does not occur in the urine under 
normal conditions. There can be no doubt, however, that the integ- 
rity of the epithelial lining of the glomeruli and the convoluted 
tubules must be regarded as the principal factor which pre vents the 
albumin of the blood from passing into the urine. When the readi- 
ness with which the glandular structure of the kidney responds to any 
abnormal stimulation is considered, it is easily understood how an 
albuminuria may be evoked in many different ways. Aside from 
acute and chronic inflammatory processes in the widest sense of the 
word, an albuminuria may be the result of circulatory disturbances 
in the kidneys of whatever kind — i.e., the result of anaemia, as well 

of hyperemia. In many and perhaps the majority of cases in 



the unix/:. 339 

which, what Bamberger terms a hasmcUogenous albuminuria occurs, 
we have direct evidence of the existence oi circulatory disturbances, 

as in cases of uncompensated valvular Lesions, weak heart, emphy- 
sema, hepatic cirrhosis, etc. In other cases, however, the existence 
of such disturbances can only be surmised, and the question whether 
or not, for example, the albuminuria observed in the various infec- 
tious diseases is referable to circulatory abnormalities, or to a direct 
irritative action of microbic poisons upon the renal parenchyma, 
must still remain an open one. 

From personal studies in connection with the functional albumi- 
nuria of Da Costa, it seems not unlikely that in many cases in which 
obscure circulatory disturbances are supposed to exist and made 
responsible for an existing albuminuria, this is referable rather to the 
strain thrown upon the kidneys by the continued elimination of 
abnormally large quantities of organic material, the quantity of water 
being at the same time proportionately small. 

If it be remembered, furthermore, that injuries affecting certain 
portions of the brain are followed by albuminuria, and that such may 
be artificially produced by a piqure, analogous to the glycosuric 
piqure of C. Bernard, still another factor is given which may pos- 
sibly enter into the causation of albuminuria. 

Obstruction to the outflow of urine from the kidneys has also 
experimentally been shown to lead to albuminuria, an observation 
with which clinical experience is in perfect accord. 

Finally, an abnormal composition of the blood may at times cause 
albuminuria. 

In passing on to a more detailed study of the various pathologic 
conditions under which an elimination of albumin may be noted, an 
attempt will be made to classify the various forms of albuminuria 
in accordance with the more general considerations set forth above. 
It should be remembered, however, as already indicated, that it may 
be very difficult, if not impossible, to assign one single cause to a 
given clinical case, as several factors may at the same time be con- 
cerned in the production of the albuminuria. 

1. Functional albuminuria. Under this heading may be com- 
prised the various forms of " physiologic" albuminuria which have 
already been considered. 

2. The albuminuria associated with organic diseases of the kidneys ; 
viz., acute and chronic nephritis, renal arterio-sclerosis, amyloid 
degeneration of the kidneys. 



340 CLINICAL I>lA<?yOSI>. 

In acute nephritis, albuminuria, usually of considerable intensity, 
is a constant and most important symptom. The amount eliminated 
- generally proportionate to the intensity of the disease, but varies 
within fairly wide limits, generally from 0.3 to 1 per cent., corre- 
sponding to a daily excretion of from 5 to 8 grammes. Much 
larger quantities, it is true, are at times excreted, but it may be 
definitelv stated that the daily loss of albumin seldom exceeds 20 
grammes. 

In chronic parenchymatous nephritis the elimination of albumin 
is likewise constant, and the amount excreted in severe cases may 
even exceed that observed in the acute form. An elimination of 
from 15 to 30 grammes, viz.. 1.5 to 3 per cent, by weight, is fre- 
quently observe:!. 

In the ordinary form of chronic interstitial nephritis the elimina- 
tion of albumin is, as a general rule, slight, rarely amounting to more 
than 2 to 5 orammes pro die. At the same time it is not unusual 
to meet with an apparent absence of the albumin, if the more com- 
mon tests (see below) be employed. If it be remembered that very 
often the diagnosis of the dis^ ase is directly dependent upon the 
demonstration of the presence or absence of albumin, the necessity 
of frequent examinations and the employment of more delicate tests, 
particularly of the trichloracetic-acid test, as well as of a careful 
microscopic examination is at once apparent. This is of even more 
moment in the renal arterio-sclerosis of Senator, in which albumin 
:he ordinary tests is probably not demonstrable in the majority 
of cases, and in which even the trichloracetic-acid test may not be 
of service, and casts absent. 

Amyloid degeneration of the kidneys, in the absence of inflamma- 
tory processes, ia accompanied by a condition of the urine closely 
resembling that observed in the ordinary form of chronic intersti- 
tial nephritis. A total absence of albumin, however, is less frequently 
noted, while an amount varying between 1 and 2 per cent, is not at 
all uncommon. It will be shown later on that in this condition con- 
siderable amounts of serum-globulin are excreted in addition to the 
serum-albumin ; larger amounts in fact than are generally observed 
in this form of chronic renal disease, so that Senator suggests :hat 
such a relation, in the absence of an acute nephritis or an acute 
exacerbation of a chronic nephritis, may be of a certain diagnostic 
value. 

3. Febrile albuminuria. That albuminuria inav occur in almost anv 



THE URINE. :\\\ 

one of the various febrile diseases is a well-known foot, but it is impor- 
tant to remember that while such an albuminuria may at times be refer- 
able to a true nephritis developing in the course of or during convales- 
cence from an acute febrile disease, such is the exception, and not the 
rule. Under this heading only that form will be considered which is 
not associated with distinct changes affecting the renal parenchyma, 
and which generally appears during the height of the disease only, to 
disappear again with a return of the temperature to normal limits. 
As has already been mentioned, it is often very difficult, if not impos- 
sible, to assign a definite cause for the occurrence of an albuminuria 
of this character, and in all probability several factors are in opera- 
tion at the same time. lu the beginning of the disease, when, as a 
rule, the blood-pressure is increased, the albuminuria may be refer- 
able to an ischsemia of the kidneys, as the increased pressure in fever, 
according to Cohnheim and Mendelson, is largely referable to spasm 
of the arterioles. Later on, or in the beginning of cases in which 
especially severe intoxication exists, the blood-pressure may be 
subnormal, and the albuminuria be due to this cause — i.e., a 
hyperpemic condition of the kidneys. As a matter of fact, it has 
been experimentally demonstrated that both anaemia and hyperemia 
of the kidney-structure may lead to albuminuria. On the other hand, 
it is not at all unlikely that the strain thrown upon the kidneys by 
an excessive elimination of organic material, in the absence of a cor- 
respondingly large quantity of water, may produce albuminuria. 
The author has repeatedly seen the functional albuminuria of the 
type described by Da Costa disappear during the administration 
of a diet relatively poor in nitrogen, where at the same time an 
increased diuresis was effected by the consumption of large amounts 
of water. 

In those grave cases of typhoid fever, furthermore, which are 
characterized by high fever and pronounced nervous symptoms, it 
would appear quite likely that the albuminuria, which in these cases 
is particularly marked, is referable to a direct influence upon the 
central nervous system, and in some cases, at least, also dependent 
upon an irritant action on the part of the microbic poisons circu- 
lating in the blood upon the renal epithelium. The character of the 
albuminuria will largely depend upon the intensity of the intoxica- 
tion j in other words, upon the amount of bacterial poison present 
at any one time in the blood. 

Notwithstanding statements to the contrary, albuminuria may be 



342 CLINICAL DIAGNOSIS. 

regarded as a constant symptom of typhoid fever, as has been defi- 
nitely demonstrated by Gubler and Robin. It is difficult to say 
why other observers found this in only a comparatively small per- 
centage of cases, but it is not unlikely that this was owiug to a lack 
of uniformity in methods, it being presupposed also that observations 
of this kind can only be decided by daily examinations. According 
to Robin, the trace of albumin which is at times observed duriug the 
first week of the disease is an albumose, while later on sernm-albu- 
min is quite constantly fonnd, the amount increasing with the inten- 
sity of the morbid process, the highest figures being reached in fatal 
cases. The more severe the disease the earlier does albumin appear 
in the urine, it being remembered, however, that reference is had 
only to those cases in which distinct renal changes are not demon- 
strable. Toward the termination of the fastigium the amount of 
albumin generally undergoes a certain diminution and may even 
entirely disappear. This diminution, however, is only temporary, 
and in severe cases the albumin again increases in amount during 
the period of the great variations in the temperature. In light cases 
an increased elimination also takes place at this stage, but is soon 
followed by a decrease, after which time only traces can be demon- 
strated in the urine. In some also it entirely disappears, but it is 
rare, according to Robin, to meet with cases in which a trace at least 
does not reappear during convalescence. 

In light cases the albuminuria rarely persists longer than the fifth 
or eighth day of convalescence, and Robin even goes so far as to say 
that a relapse may frequently be predicted, if the albuminuria does 
not disappear at this time. A limited number of personal observa- 
tions have borne out the correctness of this view, and in one case in 
which a relapse occurred as late as the fifteenth day of convalescence 
traces of albumin could be demonstrated during the entire period. 
In severe cases, on the other hand, the albumin persists for a variable 
length of time, rarely disappearing before the tenth day of convales- 
cence. At times an increase is seen during convalescence, where 
only traces have previously been observed. It is this form which 
the French generally speak of as colliquative albuminuria. While 
this form is principally observed in typhoid fever, it is not unusual 
to meet with it during the convalescence from various other acute dis- 
eases. Care must be taken not to confound the albuminuria so 
frequently seen during the convalescence from typhoid fever, referable 
to a pyelitis, with the form just described. 



THE URINE. 343 

From the following table constructed from data given in Robin's 
most excellent work on the urine of typhoid fever and other acute 
infectious diseases which may be associated with a typhoid condition, 
an idea may be formed of the occurrence of albuminuria, as well as 

of its degree of intensity in the latter diseases : 

Acute miliary tuberculosis : Albumin much less frequent than in 
typhoid fever ; when present it is rarely found in the abundance so 
characteristic of the fatal cases of the latter disease. 

Pneumonia : Albumin is as uniformly present as in typhoid fever. 
At times very abundant. 

Grippe : Albumin infrequent ; present in about 20 per cent, of 
the cases and only in traces. 

Herpetic fever : Albumin never present in large amounts. 

Eiubarras gastrique : Albumin rarely present. 

Adynamic enteritis of adults : Albumin almost always present, 
but usually only in traces. 

Cerebro-spinal meningitis : Albumin in fairly large amounts. 

Vegetative endocarditis : Albumin very abundant in about 14 per 
cent., evident in 44 per cent., and traces in 42 per cent. 

Acute articular rheumatism: Albumin present in about 40 per cent. 

Rubeola : Albumin usually absent in light cases, but present in 
the more severe and complicated forms. 

Intermittent fever : Albumin variable. 

In conclusion, it may be said that practically every acute febrile 
disease, even simple follicular tonsillitis, may be accompanied by 
albuminuria in the absence of definite changes affecting the renal 
parenchyma. Its occurrence in an individual case is probably de- 
pendent, to a very large degree, upou the intensity of the intoxica- 
tion. While it is generally an easy matter to distinguish between 
this form of albuminuria and that associated with distinct organic 
changes in the kidneys, considerable difficulty may at times be expe- 
rienced, a question which will be dealt with later on. 

4. Albuminuria referable to circulatory disturbances. To this class 
belongs the albuminuria so frequently observed in cardiac insuffi- 
ciency referable to valvular lesions, degeneration of the heart-muscle 
from whatever cause, disease of the coronary arteries, etc., as well 
as in cases of impeded pulmonary circulation affecting the general 
circulation through the right heart, and, finally, in conditions asso- 
ciated with local circulatory disturbances, such as compression of 
the renal veins by a pregnant uterus, tumors, etc. It has already 



344 <:iiy:CAZ BIAGyOSLS. 

been pointed out that febrile albuminuria also may, to a certain 
extent at least, be referable to such causes : i.e., an ischsemia or 
hyperemia of the kidneys, produced by an increased or diminished 
>d-pressure. The albuminuria observed in cases of cholera in- 
: the simpler forms of intestinal catarrh, and in cholera 
icularly, are undoubtedly dependent upon such causes. 
The occurrence : albuminuria after cold baths, as stated afc> 
is regarded by many as a ' :i physiologic " phenomenon, a view 
h should be rejected, however, as there can be but little 
that this form of albuminuria also is referable to circulatory 
disturb an t ; The quantity of albumin found under these circum- 
stances varies considerably, but rarely exceeds 0.1-0.2 per cent., 
unless indeed the disease has advanced to a point where distinct 
changes in the renal parenchyma have resulted. 

5. All :.': impeded outflow of urine. Clini- 

cally, albuminuria referable primarily to an impeded outflow of 
urine from the kidneys is probably of more frequent occurrence than 
is generally supposed, and especially in women, in whom Kelly and 
others have demonstrated the frequent existence of ureteral stenosis. 
A complete blocking : the excretory duct, on the other hand, is 
seen, but may be caused by the impaction of a renal calculus, 
die pressure of a tumor, or following certain gynaecological opera- 
- in which the ureter is accidentally caught in a suture, etc. It 
has also been suggested that the albuminuria of pregnancy may be 
due to compression of an ureter, bat it is more likely that other 
factors are here of moment, i.e., compression of :^r renal arteries, as 
well as of the veins. 

It was formerly quite gen- 
erally supposed that Bright's disease was dependent upon cer- 
tain abnormalities : the blood, a view which has n:<: :n> never 
ired, but which is actually gaining in importance from 
day fcc day, _^; ;; :;.:;._ :; Seiii'ii;:^. Bight's ii-ease is referable 
primarily to an abnormal power of diffusion on the part of the albu- 
mins of the blood which are eliminated by the kidneys as waste 
material. As a result of the excessive amount of work thus done 
definite renal changes are finally produced. According to his 
theory, then, the albuminuria is the primary factor in the causa- 
of nephritis, a view which, notwithstanding many assertions 
:ae contrary, has certainly many points in its favor. Should 
thesis n old good, Senator is correct in asserting that an 



THE URINE. 345 

albuminuria o! functional origin, so to speak, must precede the occur- 
rence of the nephritis proper. He appears to doubl the occurrence of 
a preoephritio albuminuria, however. In this connection it is inter- 
esting to note that definite renal changes have actually been observed 
to follow an apparently functional albuminuria (Da Costa), demon- 
strating the possibility of such an occurrence. Further researches, 
however, are urgently needed iu this direction, and Semmola's view, 
as well as all others so far proposed, can only be regarded as an 
hypothesis. Even if such blood-changes as those which Semmola 
suggests should not exist, there can be but little doubt that true 
nephritis is dependent upon an acute or chronic dyscrasia of the 
blood, either in the sense of an abnormal mixture of the normal 
elements or of the presence of abnormal constituents, and notably of 
poisons. The same considerations undoubtedly also apply to various 
other forms of albuminuria, iu so far as these are not the direct 
result of circulatory disturbances. 

Clinically, albuminuria of haemic origin is observed in various 
diseases of the blood, such as purpura, scurvy, leukaemia, pernicious 
anaemia, and also in cases of poisoning with lead and mercury, in 
syphilis, jaundice, diabetes, following the inhalation of ether and 
chloroform, etc. The albuminuria associated with an excessive 
elimination of uric acid and oxalic acid, and, according to personal 
observation, with an excessive elimination of organic material in 
general, notably of urea, probably also belongs to this class. 

7. Toxic albuminuria. It has already been stated that the albu- 
minuria of acute febrile diseases may to a certain extent be referable 
to a direct irritant action on the part of bacterial poisons upon the 
renal parenchyma. Poisoning with cantharides, mustard, oil of 
turpentine, potassium nitrate, carbolic acid, salicylic acid, tar, iodine, 
petroleum, phosphorus, arsenic, lead, antimony, alcohol, and mineral 
acids produces albuminuria. Iu all probability, however, the albu- 
minuria here observed is referable not only to a direct irritant action 
upon the glandular epithelium of the kidneys, but also to circulatory 
disturbances. 

8. Neurotic albuminuria. It is claimed by some that albumin, 
usually in small amounts, is eliminated in epilepsy after every attack, 
while others deny its occurrence under such conditions either entirely 
or regard it as exceptional. In a number of cases in which the author 
had occasion to examine the urine voided after an attack albumin 
was usually absent. It must be stated, however, that the seizures 
in these cases were comparatively mild, and that an examination 



346 CLINICAL DIAGNOSIS. 

for semen was unfortunately not made in those cases iu which only 
traces of albumin could be demonstrated. A recent examination of 
the urine voided by an epileptic, after having been in the epileptic 
state for more than forty-eight hours, showed the presence of a small 
amount of albumin, associated with an enormous elimination of uric 
acid, as well as a large excess of urea. Semen was absent. A 
transient albuminuria has also been noted in cases of progressive 
paralysis, mania, tetanus, delirium tremens, apoplexy, migraine, Base- 
dow's disease, etc. 1 

Although albuminuria may apparently be artificially produced 
by injuries affecting a certain point in the floor of the fourth ventri- 
cle, analogous to the production of glycosuria (see Glycosuria), it 
would probably be going too far to assume the existence of a certain 
specific centre, stimulation of which would cause the appearance of 
albumin in the urine. While the influence of the nervous system 
in preventing the passage of albumin through the glomeruli under 
normal conditions is undoubted, it would appear more likely that 
the albuminuria following injuries to the central nervous system is 
referable to circulatory disturbances in the kidneys secondary to 
lesions in the brain, especially in the medulla. The albuminuria 
observed in certain neurotic individuals, on the other hand, is prob- 
ably more frequently associated with metabolic abnormalities and 
of hsemic origin. 

9. A digestive albuminuria has also been described, but need not 
be considered in detail. Suffice it to say that it may follow the in- 
gestion of excessive amounts of cheese, eggs — particularly when taken 
raw — beef, etc. The author has seen albuminuria follow a free in- 
dulgence in root beer. It is, of course, difficult to explain such 
occurrences ; but, beariug in mind the fact that albuminuria very 
often follows the ingestion of such articles almost immediately and 
before they have actually had time to become absorbed, it is hardly 
justifiable to refer this form to the existence of a hyperalbuminosis. 
It would appear more rational in such cases, as Senator has sug- 
gested, to think of reflex or vasomotor or trophic changes affecting 
the kidneys ; while in other cases, in which the albuminuria does 
not follow the ingestion of such articles of food immediately, it is 
quite probable that this may be dependent upon certain metabolic 
abnormalities affecting the normal composition of the blood. 2 

1 Recently the author observed the occurrence of albumin in the urine of a case of cerebral 
sarcoma. 

2 The albumin which is eliminated after the ingestion of much egg-albumin, however, does 
not belong to this category. 



THE URINE, 347 

Iu the account given of the occurrence of albuminuria and its 
possible causes reference has been only had to a purely renal albu- 
minuria. It should be remembered, however, thai the origin of the 
albumin may often be extremely difficult to determine, as albumi- 
nous material, such as blood and pus, may become mixed outside of the 
glandular portion of the kidneys with what would otherwise have 
been a perfectly normal urine, and that such an admixture may not 
ouly take place in the ureters, the bladder, and the urethra, but 
even in the pelvis of the kidney. 

The term accidental albuminuria is applied to a condition in which 
albuminous material becomes mixed with a urine beyond the kidneys 
which has been secreted free from albumin, as in cases of cystitis and 
urethritis, or whenever semen has entered the urine. Such an admixture 
of pus, blood, lymph, or chyle may, however, occur in the kidneys, 
when the albuminuria is termed accidental renal albuminuria, an ex- 
ample of which is frequently seen in the slight degree of albuminuria 
referable to pyelitis, during the convalescence from typhoid fever. By 
a mixed albuminuria aud a mixed renal albuminuria, on the other 
hand, are meant conditions in which the source of the albumin is 
twofold, renal and extrarenal in the first instance, parenchymal 
and extraparenchymal in the second, examples being the albuminuria 
of cystitis combined with nephritis and pyelonephritis, respect- 
ively. 

It is manifest, of course, that in every instance in which albumin 
is found in the urine its origin should be ascertained. While this 
question is usually readily decided by a microscopic examination of 
the urine, considerable difficulty may occasionally be experienced. 
It is a well-known fact that in the urine of females a trace of albu- 
min may frequently be detected which is not due to any existing 
lesion of the urinary organs, but to an admixture of vaginal dis- 
charge, of blood during the process of menstruation, and in married 
women of semen. Whenever, therefore, doubt is felt as to the 
origin of the albumin, the specimen for examination should be ob- 
tained by the catheter, care being taken previously to cleanse the 
vulva. In males albumin may be referable to a gonorrhceal ure- 
thritis, and only recently a case was observed in which a gentleman, 
who had been rejected by a life-insurance examiner on account of the 
presence of albumin in his urine, was discovered to have a free 
urethral discharge, the albuminuria clearing up on treatment of his 
gonorrhoea. In such cases it is well to let the patient flush out 



348 CLINICAL DIAGNOSIS. 

his urethra first, and make use of the portion last passed for exami- 
nation. Very often the conditions are more complex, it being un- 
certain whether the albumin is due to a cystitis or whether it has 
come from the kidneys. Here a careful microscopic examination is 
called for and will in the majority of instances decide the question. 
At other times even then we may be left in doubt, when recourse 
should be had, if at all possible, to catheterization of the ureters. 
The latter procedure is usually called for in obscure cases of pyuria 
and of hematuria, in which it is not only necessary to ascertain the 
origin of the pus or blood, but to determine the kidney from which 
this has proceeded, and, if one be found to be diseased, the condition 
of the other. 

As far as the amount of albumin which may be eliminated in the 
twenty-four hours is concerned, an excretion of less than 2 grammes 
may be regarded as insignificant, 6 to 8 grammes as moderate, and 
10 to 12 grammes or more as excessive. An excretion of 20 to 30 
grammes must be considered as very exceptional. An elimination 
of more than this amount probably never occurs. 

Other albumins which may occur in the urine at times, as already 
indicated, are serum-globulin, albumoses, viz., peptones, hseruoglobin, 
fibrin, mucin (nucleo-albumin), and histon. 

Serum-globulin. It has been pointed out that serum-globulin is 
found in the urine together with serum-albumin in large amounts in 
cases of amyloid degeneration of the kidneys, and, according to 
Senator, a ratio between the amounts of these two albumins of 
1 : 0.8 : 1.4 may be regarded as a fairly constant symptom of this 
disease, and of some diagnostic importance. There seems to be no 
doubt, however, that serum-globulin occurs in the urine, although 
in much smaller quantities than in the disease mentioned, whenever 
serum-albumin is eliminated, and so far not one case of pure globu- 
linuria has been reported, a fact which is not surprising, as there 
is no reason why only one albumin present in the blood should pass 
through the kidneys. 

Albumoses (peptones). The presence of albumoses in the urine 
has frequently been observed, but is probably more frequently over- 
looked, as the bodies in question are not precipitated upon boiling. 
The factors which cause their appearance in the urine are probably 
similar to those noted in connection with peptonuria, and will be 
presently considered. Suffice it to say that albumoses have been 
observed in a variety of diseases, such as multiple myelomata of the 



THE URINE, 349 

bones, dermatitis, intestinal ulceration, Liver-abscess, croupous pneu- 
monia, septicaemia, carcinomatous peritonitis, apoplexy, heart-disease, 
pleurisy, caries, puerperal parametritis, endocarditis, typhoid lever, 

nephritis, phthisis, measles, scarlatina, leukaemia, urticaria, acute 
yellow atrophy, various psychoses, eta Very frequently albumos- 
uria accompanies albuminuria, a condition which has been termed 
mixed albuminuria by Senator. In this connection it is interesting 

to note that albumosuria may alternate with albuminuria, and pre- 
cede as well as follow the latter, so that in any case in which albu- 
moses are demonstrable in the nriue the appearance of albumin 
should be expected. 

Albuminous bodies which could not be coagulated by heat, and in 
their general behavior resembled peptones, have repeatedly been seen 
in urines, when Hofmeister's method of testing for peptones was 
employed, and various forms of so-called peptonuria have since been 
described. An elimination of such bodies was noted in conditions 
associated with large accumulations of pus within the body, it being 
supposed that the peptonuria observed in such cases was referable 
to a disintegration of the pus-corpuscles and a resorption into the 
blood of the peptone contained in these. This form of peptonuria 
was hence termed pyogenic peptonuria. A hepatogenic form was 
likewise described in connection with diseases of the liver, notably 
acute yellow atrophy. It was formerly thought that peptones were 
retransformed, so to speak, into albumins by the liver, and the 
occurrence of peptonuria in diseases of this organ hence explained 
by the inability on its part to cause this transformation, the pep- 
tones accumulating in the blood and being excreted in the urine. 
Later researches, however, have shown that the transformation of 
peptones into albumins takes place in the intestinal mucosa, and that 
the liver apparently plays no part in this process, so that an explana- 
tion of this form is still wanting. An enterogenic form has been 
noted in various diseases of the intestinal tract, such as typhoid 
fever, tuberculous ulceration, carcinoma, etc., in which it was sup- 
posed that peptone is either directly absorbed from the disintegrating 
pus, or that the intestine itself has lost the power of causing its 
transformation into albumin. A histogenic or hcematogenic origin 
was further ascribed to the peptonuria seen in cases of scurvy, 
various forms of poisoning, during the puerperal period, pregnancy, 
particularly following the death of the foetus, in various psycho 
etc. Finally, a renal and vesical form of peptonuria was noted in 



350 CLINICAL DIAGNOSIS. 

which peptones were formed in albuminous urines either in conse- 
quence of the presence of enzymes or the occurrence of putrefaction. 

AI:> re recently, however, since our conception of the nature of 
peptones has changed — it being quite generally accepted at the present 
day that true peptones are not precipitated by ammonium sulphate — 
investigations have shown that in all cases in which the presence of 
these bodies had been previously assumed true peptones are actually 
not present, but that the bodies in question are propeptones or albu- 
mose-. According to Kuhne' s definition of peptones, a peptonuria 
hence loes not jxist. 

In the differential diagnosis of suppurative meningitis a posi- 
tive peptone-reaction in the older sense of the word, according to 
Senator, speaks strongly in favor of the existence of this disease, a 
point which at times may undoubtedly be of great importance. In 
support of this view he cites the case of a young man. the subject 
of a median otitis of long standing, in which symptoms pointing 
to a meningitis — viz.. fever, headache, and pains in the neck — 
were present, but in which no " peptonuria" was found to exist, 
and in which an operation revealed the presence of a cholesteatoma. 

Haemoglobin. Under normal conditions the disintegration of 
red blood-corpuscles constantly taking place in the body never re- 
sults in such a degree of hremoglobinamiia as to be followed by an 
elimination of haemoglobin in the urine, TThenever for any reason the 
destruction of red corpuscles is so extensive, however, that the liver is 
unable to transform into bilirubin all the blood-coloring matter set 
free, hemoglobinuria will occur. "While these factors, then — i. e., 
an excessive destruction of the red blood-corpuscles and. an insuffi- 
ciency on the part of the liver — must be regarded as explaining 
every case of hemoglobinuria, our knowledge of the ultimate causes 
of such excessive disintegration, as well as the manner in which 
these operate, is as yet very limited. Formerly the term hcematin- 
uria was applied to this condition. It was shown, however, that 
the pigment eliminated is in reality not ha?matin, but usually metha?- 
moglobin and only at times haemoglobin, so that the term haemoglo- 
binuria is also, to a certain extent, ill chosen. 

Most frequently to be observed, perhaps, is the hemoglobinuria 
produced by certain poisons, such as potassium chlorate, arseni- 
uretted hydrogen, sulphuretted hydrogen, pyrogallic acid, naphthol, 
hydrochloric acid, tincture of iodine, carbolic acid, carbon monoxide, 
etc., and also by morels (Helvetia esculents . 



THE URINE. 351 

Quite familiar is the hemoglobinuria observed following trans- 
fusion of the blood of animals into man, such as thai oi the calf and 
lamb ; also the form seen in eases of extensive burns and insolation. 

While hemoglobinuria may occur in the course of any one of the 
specific infectious diseases, such as scarlatina, icterus gravis, variola 
hemorrhagica, typhoid fever, yellow fever, etc., it is said to be espe- 
cially frequent in cases of malarial intoxication. This view is not 
accepted by many, Osier, among others, thinking that it has frequently 
been confounded with malarial hematuria. The author has never seen 
a single instance of malarial hemoglobinuria. On the other hand, 
there can be no doubt, to judge from the literature upon the sub- 
ject, that syphilis may, under certain conditions, be a potent factor 
in the production of hemoglobinuria. This appears to be particu- 
larly true of cases of so-called paroxysmal hemoglobinuria, a condi- 
tion in which bloody uriue is voided from time to time, the attacks 
being frequently preceded by chills and fever, so as closely to simu- 
late malarial fever. Other factors also, notably cold, appear to be 
concerned in the production of this form. 

The occasional occurrence of hemoglobinuria in cases of Ray- 
naud's disease, coincident with attacks of an epileptiform character, 
has been referred to in the chapter on Blood. (See p. 33.) 

In a case of leukemia complicated by icterus hemoglobinuria 
has been observed. 

Finally, an epidemic hemoglobinuria has been described as occur- 
ring in the newborn, associated with jaundice, cyanosis, and nervous 
symptoms; of its causation, however, we are still in profound ignorance. 

While hemoglobinuria is fairly uncommon, hematuria is fre- 
quently observed, and will be considered later on, as its recogni- 
tion is not dependent upon the demonstration of the albuminous 
body, " hemoglobin," alone in the uriue, but upon the presence of 
red corpuscles, which in hemoglobinuria are either absent or present 
in only very small numbers. 

Fibrin. The occurrence of fibrin in the urine presupposes the 
presence of fibrinogen, a fibrinogenic ferment, and probably also serum- 
globulin, and is seldom seen. According to Neubauer and Vogel, 
the fibrin may occur either as coagulated fibrin or in solution. In 
the former condition it is at times observed in the form of blood- 
coagula, when its significance is essentially the same as that of hema- 
turia in general, although it must be remembered that the usual 
form of hematuria is not associated with the presence of coagula. 



352 CLINICAL DIAGNOSIS. 

Colorless coagulaof fibrin are only seen in cases of chyluria, or diph- 
theritic inflammation of the urinary passages. On the other hand, 
urines containing fibrin in solution are likewise seen, but rarely, and 
are characterized by the fact that fibrinous coagula separate out only 
on standing, when they usually cover the bottom of the vessel, but 
inay at times change the entire bulk of urine into a gelatinous-look- 
ing mass. So far this condition has been observed only in cases of 
chyluria (which see). 

Nucleo-alburnin. It has long been known that a body is occa- 
sionally present in the urine which is precipitated by acetic acid and 
is insoluble in an excess, but soluble in nitric acid,and which apparently 
belongs to the class of albumins. This substance has been variously 
viewed as mucin, as a mucinous body, as a globulin, and recently 
as a nucleo-alburnin. Reissner, who first drew attention to its pres- 
ence in urine, found it in pneumonia, pleurisy, typhoid fever, inter- 
mittens, meningitis, cystitis, acute mania, following epileptic seizures 
etc., and regarded it as mucin. The first direct observations on the 
presence of nucleo-alburnin were made by Obermeyer, who claims 
to have found it in thirty-two icteric urines without exception, 
and also in eight cases of diphtheria, in three of which the urine 
was at the same time albuminous, and in traces in four cases of 
nephritis following scarlatina, while in other forms of Bright ; s 
disease it could only be exceptionally detected. Occasionally nucleo- 
alburnin was also found in cases of scarlatina without nephritis, in 
cases of poisoning with aniline and illuminating-gas, during the treat- 
ment of patients with pyrogallol, naphthol, and corrosive sublimate, 
and in two cases of cystitis and four cases of leukaemia. More re- 
cently still nucleo-albuminuria has been said to be not only of fre- 
quent, but even of constant occurrence, demonstrable in every urine, 
by means of the trichloracetic acid test. Personal observations, 
however, have demonstrated beyond a doubt that a positive " tri- 
chloracetic acid reaction " never occurs in the urine of perfectly 
healthy individuals, and as the result of several tnousand obser- 
vations in this direction the author can definitely state that a 
physiologic nucleo-albuminuria discoverable by this reagent is an 
illusion. With these results those obtained by Sarzin, working 
under Senator, are in perfect accord, since in 200 urines which he 
examined the presence of nucleo-alburnin could not be demonstrated 
with certainty in a single instance, the cases examined embracing 
almost the entire list of diseases usually seen in hospitals. Contrary 



THE URINR 353 

results undoubtedly depend upon a lack oi proper precautions, in 
using unfiltered or carelessly filtered urines, improper methods, etc., 
the nncleo-albuminuria in such eases being referable to disintegrating 
cells from the vagina aud urethra, as well as the bladder, ureter, and 
kidneys. A purely renal nudeo-albuminuria — /. e., an elimination 
of nucleo-albumin from the blood through the kidneys — does not 
exist. 

In this connection it may not be out of place to insist upon the 
importance of employing carefully filtered urine, and fresh urine of 
an acid reaction, in determining the value of reagents proposed for 
the detection of true albumin. 

Histon. Quite recently Kolisch and Burion were able to demon- 
strate the presence of histon in the urine of a case of leukaemia, an 
albuminous body which was first discovered by Kossel in the red 
blood-corpuscles of the goose, and which was shown to exist in the 
leucocytes of human blood in combination with the acid leuko- 
nuclein, constituting the so-called nucleo-histon of Lilienfeld. Ac- 
cording to these observers, the substance was always present in their 
case. The method which they employed in testing for its presence 
was the following : 

The urine of twenty-four hours was first examined for albumin, 
and this removed, if present. It was then precipitated with 94 per 
cent, alcohol, the precipitate washed with hot alcohol and dissolved 
in boiling water. Upon cooling, the solution thus obtaiued was 
acidified with hydrochloric acid and allowed to stand for several 
hours. During this time a cloudiness, referable to a large extent to 
uric acid, develops, which is filtered off, when the filtrate is precipi- 
tated with ammonia. In addition to certain mineral constituents, 
histon, if present, is also thrown down. The precipitate is collected 
upon a small filter and washed with ammoniacal water until the 
washings no longer give the biuret reaction. It is then dissolved in 
dilute acetic acid and the solution tested with the biuret test ; if this 
yields a positive result, and if coagulation occurs upon the applica- 
tion of heat, the coagulum being soluble in mineral acids, the presence 
of histon may be inferred. 

It is not clear in what manner the histonuria is produced ; so 
much, however, seems certain, that it is not solely dependent upon 
the increased destruction of leucocytes. 

Tests for Albumin. The recognition of the various albuminous 
bodies which may occur in the urine is based partly upon their 

23 



354 



CLINICAL DIAGNOSIS 



Fig. 92. 



direct precipitation and partly upon color-reactions when treated 
with certain reagents. 

The number of tests which have from time to time been suggested 
is very large ; many of them, after a brief period of use, have been 
discarded as useless or uncertain, while others have been employed 
only occasionally and have not received the recognition which they 
deserved from the fact that simpler tests existed, that they did not 
possess sufficient delicacy, or that in some instances it was too great. 
In the following pages no attempt will be made to describe all of 
these tests, and attention will be directed only to those which are 
generally used and which clinical experience has proved to be of 
value, precedence being given to those which have been longest in 
use. While some of these are applicable for demonstrating the 
presence of more than one form of albumin, special tests will also be 
described whereby the various albumins may be individually recog- 
nized. 

In every case the urine should be carefully filtered, so as to free 
it from any morphologic constituents, etc., present. To this end it is 

generally sufficient to pass the 
urine through one or two layers 
of Swedish filter-paper. Fre- 
quently, however, a clear speci- 
men cannot be obtained in this 
manner ; it is then advisable to 
shake the urine with magnesia 
usta, or to mix it with scrapings 
of filter-paper, when it is filtered 
as usual. 

Tests for Sertjm-albumix. 
The nitric- acid test. (Fig. 92.) 
The value of this test, properly 
applied, cannot be overestimated, 
as it is not only simple, but yields 
an amount of information that 
can otherwise only be gained with 
difficulty ; information, moreover, 
which is valuable in many re- 
spects. Usually the student is 
advised to make use of a test-tube partially filled with urine, along 
the sides of which concentrated, chemically pure nitric acid is allowed 




Nitric-acid test. 



PLATE VIII. 



FIG. 2. 



FIG. 4. 





-*# 




FIG. 1. 




FIG. 3. 






FIG. S. 








Fig. i. The Xitric-Acid Test as applied to the Urine : The light, color- 
less ring in the clear urine above shows a slight increase in the amount of 
uric acid ; the large white band denotes a large amount of albumin, border- 
ing upon a colored ring, referable partly to indican (blue) and partly to 
urorosein. 

Fig. 2. The Nitric-Acid Test as applied to the Urine : The light ring in 
the clear urine above denotes a slight increase in the amount of uric acid. 
The bluish-black band is referable to an enormous increase in the amount 
of indican. Taken from a case of ileus. 

Fig. 3. The Nitric-Acid Test as applied to the Urine: The broad, light 
band in the clear urine above is referable to an enormous increase in the 
amount of uric acid. 

Fig. 4. The Nitric-Acid Test as applied to the Urine : The color play 
referable to the presence of bilirubin is shown in a schematic manner. 

Fig. 5. The Nitric-Acid Test as applied to the Urine : The colored ring 
is referable to the presence of normal urinary coloring matter. 



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THE URINE, 355 

to flow, so as to form a layer at the bottom of the tube, when in the 
presence of serum-albumin a distinct white cloud will appear in the 
form of a ring at the zone of contact between the two liquids (Hel- 
ler's test). The pictures thus obtained cannot be compared, however, 
with those seen when the apparently trivial change is made oi using 
a conical glass of about 2 ounces capacity instead of the test-tube. 
About 20 c.c. of urine are placed in the glass, and 6 to 10 c.c. of 
nitric acid added by means of a pipette, which is carried to the bot- 
tom of the vessel, when the acid is slowly allowed to escape by dimin- 
ishing the pressure of the finger upon the tube. When this is 
carefully done, as in Heller's test, the nitric acid forms a distinct 
zone beneath the urine. In the presence of albumin the cloud re- 
ferred to above will be seen, its extent and intensity varying with 
the amount of albumin present. (Plate VIII., Fig. 1.) If now the 
glass be allowed to stand for some time — and if small amounts 
be present, these only appear on standing — it will be observed that 
gradually the cloudiness extends upward, the upper border of the 
albumin-ring, with few exceptions, being at first as well defined as 
the lower border, when the coagulated albumin may be seen to rise 
into the supernatant liquid in the form of small, irregular columns. 
This appearance may possibly be referable to the partial decomposi- 
tion of uric acid by means of nitric acid, nitrogen and carbon dioxide 
being set free, which, rising to the surface in the form of small bub- 
bles, carry the nitric acid upward ; this coming into contact with 
albumin in solution then causes the precipitation of the latter. An 
excess of uric acid, moreover, is indicated by the appearance, within 
five to ten minutes after the addition of the nitric acid, of a distinct 
ring in the clear urine about 1 to 2 cm. above the zone of contact, 
which is similar in appearance to that due to albumin. If this ring 
(Plate VIII , Figs. 1, 2, and 3), which has been very appropriately 
compared to a holy wafer, does not appear within five to ten minutes, 
it may be assumed that the uric acid is present in diminished amount ; 
on the other hand, it is possible to determine the degree of increase 
by the size of the ring, it being presupposed that the same quanti- 
ties of urine and of the reagent are employed in every case. 

Should more than 25 grammes of urea be contained in a liter of 
the urine examined, an appearance like hoarfrost will be noted on 
the sides of the vessel due to the formation of urea nitrate, while 
spangles of the same substance only appear in the presence of at least 



356 CLINICAL DIAGNOSIS. 

45 grammes. Should 50 grammes or more of urea be contained in 
the liter, a dense mass of urea nitrate may be seen to separate out. 

Biliary urine when treated with nitric acid containing a little 
nitrous acid shows the color-play referable to the action of nitric 
acid upon bilirubin | Fig. 4, Plate VIII.), the production of the colors, 
yellow, green, blue, violet, and red, taking place from above down- 
ward, the green color being the most characteristic ; in the absence 
of the latter the presence of biliary pigment may be positively ex- 
cluded. The presence of albumin is not at all objectionable, as the 
color-play takes place beneath the albuminous disk. 

In normal urine a transparent, colored ring is also obtained, pre- 
senting a peach-blossom red, the intensity of which, however, may 
vary from a faint rose to a pronounced brick color, referable to 
normal urinary pigment. (Fig. 5, Plate VIII ) In the presence 
of urobilin, on the other hand, this ring presents a distinct mahog- 
any color. 

Indican is indicated by the appearance of a more or less violet 
ring (Fig. 2, Plate VIII) situated above that referable to the normal 
urinary pigment, its intensity varying with the amount present, 
from a light blue to a deep indigo-blue, which may color the entire 
urine when this is shaken. 

A cloud at the zone of contact of the two fluids may be referable 
not only to the presence of serum-albumin, but also of globulin and 
albumoses (propeptones), while a negative reaction will generally 
indicate the absence of these bodies. That the uric-acid ring will 
be mistaken for albumin is hardly likely, if it be recollected that 
this never first appears at the zone of contact of the two fluids, but 
always in the uppermost portion of the urine. It is true that urines 
are occasionally observed in which the separation of uric acid, always 
in the amorphous form, takes place so suddenly that within a minute 
or two the entire urinous portion of the mixture is completely 
clouded, resembling the appearance presented by a highly albuminous 
urine. Such an excessive elimination of uric acid is quite uncommon, 
nowever, and it is to be remembered that with uric acid the cloudiness 
proceeds from above downward, and never from below upward, as 
is the case with albumin. Should ^any doubt be felt, it is only 
necessary to remove a few c.c. of this cloudy urine by means of a 
pipette and heat them gently in a test-tube, when the urine will 
clear up entirely if the precipitate be due to uric acid, while if caused 
bv albumin it will remain or become still more intense. Should the 



THE URINE. 357 

precipitate caused by nitric arid consist oi albumoses, this will also 
clear up entirely, to reappear on cooling, the fluid at the same time 
assuming a distinct yellow color. The occurrence of a distinctly 
yellow color in a urine, moreover, which is only partially cleared 
upon the application of heat, and be it remembered that a much 
higher temperature is necessary for the solution of a precipitate re- 
ferable to albumoses than of one due to urates, will indicate the 
existence of a mixed albuminuria ; /. c, the presence of coagulable 
albumin and albumoses. Nitric acid may also cause a precipita- 
tion of certain resinous bodies, such as those contained in turpen- 
tine, balsam of copaiba and tolu, etc. If any doubt be felt, the 
mixture should be shaken with alcohol, when the precipitate caused 
by these substances is at once dissolved. The mucinous body — 
nucleo-albumin — which is at times found in the urine, is also pre- 
cipitated by nitric acid, but need not occupy our attention at this 
place. From what has been said it is manifest that the employment 
of the nitric-acid test in the manner indicated furnishes much valu- 
able information, and the adoption of the method, as described, not 
only by hospital students, but by general practitioners as well, cannot 
be too strongly urged. 

Boiling-test. A few c.c. of urine are boiled in a test-tube and 
then treated with a few drops of concentrated nitric acid, no mat- 
ter whether a precipitate has occurred ujon boiling or not. If 
albumin be present, this will separate out as a flaky precipitate, 
which consists of serum-albumin frequently mixed with serum-glob- 
ulin. It is true that albuminous urines will generally yield a pre- 
cipitate on boiling alone, but it must be remembered that unless 
the reaction be decidedly acid, a precipitation of normal calcium 
phosphate may occur owing to the fact that the reaction of the urine 
upon boiling becomes less acid, probably owing to an escape of the 
carbonic acid held in solution. In urines presenting an alkaline or 
amphoteric reaction this is very frequently noted and might give rise 
to confusion, as the precipitate due to calcium phosphate very 
closely resembles that due to albumin. Care must hence be taken 
to insure a distinctly acid reaction, which is best accomplished by 
the addition of nitric acid, when a precipitate referable to phosphates 
is at once dissolved, while one due to albumin remains and may 
even become more marked. The quantity to be added should usually 
be equivalent to about 0.05 to 0.1 of the volume of the urine, and 



358 CLINICAL DIAGNOSIS. 

under no consideration should the acid be added before boiling, nor 
should the urine be boiled after its addition, as small amounts of albu- 
min will otherwise be overlooked, owing to the fact that hot nitric 
acid dissolves the precipitate to a certain degree. If after the addi- 
tion of the nitric acid the urine turns a distinct yellow, and if then 
upon cooling a white precipitate appears, the presence of albumoses 
may be inferred. Uric acid will probably never cause confusion, as 
this only separates out upon cooling, and then presents a dark-brown 
color. As in the case of the nitric-acid test, so also here, a pre- 
cipitation of certain resins is noted at times, which may, however, be 
recognized by their solubility in alcohol. 

Should acetic acid be used instead of nitric acid, great care must 
be taken to avoid an excess, as otherwise the albumin will be dis- 
solved. As this danger diminishes the greater the quantity of salts 
contained in the urine, it is advisable to treat the urine first with 
a few drops of acetic acid until a distinctly acid reaction is obtained, 
and then to add one-sixth of its own volume of a saturated solution of 
sodium chloride, magnesium sulphate, or sodium sulphate, when upon 
boiling a precipitation of the albumin will take place. Carried out 
in this manner, the test is absolutely certain and will demonstrate 
even minimal amounts of albumin. 

The potassium ferrocyanide test. A few c.c. of urine are strongly 
acidified with acetic acid (sp. gr. 1.064) and treated with a few drops 
of a 10 per cent, solution of potassium ferrocvanide, when in the 
presence of but little albumin a faint turbidity, or, if much albumin 
be present, a flaky precipitate, is noted, which is best recognized by 
comparison with a tube containing some of the pure filtered urine, 
both tubes being held against a black background. Concentrated 
urines should be previously diluted with water, as propeptones, like 
serum-albumin and serum-globulin, which may be precipitated in this 
manner, otherwise remain in solution. Here, also, as in the tests 
described, the presence of propeptones may be inferred if the pre- 
cipitate disappears upon boiling, while a partial clearing up, on the 
other hand, indicates the presence of both albumoses and coagulable 
albumin. 

At times the addition of acetic acid by itself is followed by the 
appearance of a cloud in the urine, which may be due to urates or 
to urinary mucin (nucleo-albumin), as already mentioned. In such 
cases the urine should be refiltered and diluted with water and the 
test again applied. 



THE hum: 359 

a'. Jaksch advises the careful addition, by means oi a pipette, oi 

a few c.e. oi' fairly concentrated acetic acid to which a little potas- 
sium ferrocyanide has been added, when the albumin, as in Heller's 
test, is seen to form a ring at the surface of contact between the two 
fluids. Instead of potassium ferrocyanide, potassium platinocyanide 
may also be employed, and has the advantage that the test-solution 
is colorless. 

The trichloracetic acid test. This test is undoubtedly the most 
delicate of those so far described, but not so delicate that a trace of 
albumin, or nncleo-albnmin, as has been suggested by some, can be 
demonstrated in every urine. An experience based upon the exami- 
nation of several thousand urines with this reagent warrants the 
author's speakiug with a certain amount of confidence upon the sub- 
ject. Very frequently it is thus possible to demonstrate albumin in 
urines in which the more common tests yield negative results, but 
in which tube-casts may nevertheless be found upon microscopic ex- 
amination. The test is applied as follows : By means of a pipette, 1 or 
2 c.c. of an aqueous solution of the reagent (sp. gr. 1.147) are carried 
to the bottom of a test-tube containing the carefully filtered urine, so 
as to form a layer beneath the urine, when, in the presence of albu- 
min, a white ring will be seen to form at the zone of contact between 
the two fluids, varying in intensity with the amount of albumin 
present. As far as the test for albumin is concerned, this reagent 
possesses an advantage over the nitric acid in that the colored rings, 
so often confusing to the inexperienced, are but rarely observed. 
Serum-albumin, serum-globulin, and albumoses are thus precipitated, 
the presence of the latter being recognized, as in the previous tests, 
by the fact that the precipitate disappears upon boiling, to reappear 
again upon cooling. A cloud, referable to uric acid, also appears if 
this be present in excessive amounts, but it is readily distinguished 
from that caused by albumin by the fact that it disappears upon 
the application of gentle heat. Furthermore, a previous dilution of 
the urine guards against this occurrence. 

Other tests have also been suggested for the detection of albumin 
in the urine, such as the meta-phosphoric-acid test, the phenol, 
tannic-acid, and picric-acid tests, that with Tanret's reagent, phos- 
photungstic and phosphomolybdic acids, and quite recently Spieg- 
ler's reagent. 

Of these, only the picric-acid and Spiegler's tests will be con- 
sidered. 



360 CLINICAL DIAGNOSIS. 

Picric-acid test. The picric-acid test is not applicable as a test for 
albumin as such, and is only mentioned in this connection because 
Esbach's quantitative method is based upon it. His reagent is com- 
posed of 10 grammes of picric acid and 20 grammes of crystallized 
citric acid, dissolved in a liter of distilled water. If to this solution 
albuminous urine be added, the mixture is rendered turbid, and after 
some time a sediment which consists not only of albumins, but also 
of uric acid, kreatinin, and other extractives, will form at the bottom 
of the tube. (See Quantitative determinatiou of albumin.) 

Spiegler's test. Spiegler's reagent consists of 8 parts by weight of 
mercuric chloride, 4 parts of tartaric acid, and 200 parts of water, in 
which 20 parts of cane-sugar are further dissolved so as to increase 
the specific gravity of the reagent and permit of its being employed, 
like Heller's test, in even concentrated urines. One-third of a test- 
tube is filled with the reagent, and the urine carefully placed above 
this by allowing it to flow slowly down the side of the tube ; in the 
presence of albumin, a sharply defined white ring will be observed 
where the two liquids are in contact. Peptone gives no reaction, 
while albumoses are precipitated and may be recognized as indicated 
above. 

Special test for serum- albumin. Should it be desired, for any 
reason, to demonstrate serum-albumin alone, the urine is rendered 
amphoteric or faintly alkaline with sodium hydrate, and then satu- 
rated with magnesium sulphate in substance, in order to remove any 
globulin. The filtrate is strongly acidified by means of acetic acid, 
when a flaky precipitate, appearing upon boiling, will indicate the 
presence of serum-albumin. 

Very often, as in the examination for sugar, it is necessary to 
remove any coagulable albumin that may be present, to which end 
the urine is rendered distinctly acid with acetic acid and boiled. 
An examination of the filtrate with potassium ferrocyanide, if the 
amount of acetic acid added was just sufficient, will then yield a 
negative result (see p. 362). 

Quantitative Estimation of Albumin. For the quantita- 
tive estimation of albumin a number of methods have been devised, 
which fact in itself is sufficient to indicate that the majority of these, 
at least, are unsatisfactory. 

Old method by boiling. If only comparative results are to be 
obtained, the old method of boiling a definite amount of urine, after 
the addition of acetic acid, and allowing the albumin to settle for 



THE URINE. 



36] 



Fig. 93. 



twenty-four hours, may be employed. For this purpose tfeubauer 
suggests the use of glass tubes measuring one-hall' to three-quarters 
of au inch in diameter, closed at the lower end with a cork, into 
which the urine is poured. Ordinary test-tubes answer the purpose 
perfectly well, but care should be taken that the same quantity of 
urine be used in every case. These tubes may then be corked and 
kept for several days for comparison. Of course, the results ob- 
tained express only the relative amount of albumin present, and it 
should be remembered that the errors incurred may amount to as 
much as 30 or even 50 per cent., when compared with those obtained 
gravimetrically, owing to the fact that sometimes the albumin sepa- 
rates out in large flakes, and at other times in small flakes, and that 
the degree of precipitation is also influenced by the specific gravity 
of the supernatant urine. 

EsbacN s method. For clinical purposes, Esbach's method is the 
most convenient. As stated above, his reagent is composed of 10 
grammes of picric acid and 20 grammes of citric acid, 
dissolved in 1000 c.c. of distilled water. Special tubes, 
termed albuminimeters (Fig. 93), are employed which 
bear two marks, one, U, indicating the point to which 
urine must be added, and one, i?, the point to which the 
reagent is added. The lower portion of the tube up to 
U bears a scale reading from 1 to 7. The tube is filled 
to IT with the filtered albuminous urine, and the reagent 
added until the point R is reached. The tube is then 
closed with a stopper, inverted twelve times, and set aside 
for twenty-four hours. At the expiration of this time 
serum-albumin, serum-globulin, and peptones, as well as 
uric acid and kreatinin, will have settled down, when 
the amount pro mille in grammes may be directly read 
off from the scale. A few precautions must, however, 
be observed in order to obtain as accurate results as pos- 
sible. The reaction of the urine should be acid, and if 
such be not the case acetic acid is added. Its specific 
gravity should, furthermore, not exceed 1.006 or 1.008, 
the proper density being obtained by diluting with water. The tem- 
perature also appears to play an important rdle, the reading gener- 
ally being higher with a low than with a more elevated temperature, 
15° C. being best adapted to our purposes. 

The differential density method. More accurate results may be 



362 CLIXICAL DIAGXOSIS. 

obtained with the following method, which is based upon the dimi- 
nution in the specific gravity of the urine after the removal of all 
albumin, and its comparison with the specific gravity observed 
before. To this end the urine is treated with a sufficient amount 
of acetic acid to insure a complete precipitation of the albumin (see 
below), when its specific gravity is noted. It is then brought to 
the boiling-point, care being taken to guard against evaporation 
by placing the urine in an ordinary medicine- bottle, closing this 
with a rubber stopper that has been previously boiled in a sodium 
hydrate solution and washed until free from an alkaline reaction, 
the stopper being tightly fastened with a cord or wire. Thus pre- 
pared, the bottle is kept in boiling water for ten to fifteen minutes, 
the urine filtered upon cooling, evaporation being again carefully 
guarded against by filtering into a bottle through a funnel which 
has been passed through a closely fitting stopper, the funnel being 
kept covered by a plate of glass, when the specific gravity is again 
determined, it being best in both cases to use a pyknometer. The 
decrease in the specific gravity, multiplied by 400, will indicate 
the number of grammes of albumin contained in 100 c.c. of urine. 

Gravimetric method. If special accuracy be required, the amount 
of albumin must be determined gravi metrically as follows : A cer- 
tain amount of urine, after having been acidified with acetic acid to 
such a degree as to insure a complete separation of all albumin, is 
boiled ; the albumin is then filtered off, dried, and weighed. For 
this purpose, 500 to 1000 c.c. of carefully filtered urine should be 
available. A specimen of this, if already acid, is placed in a test- 
tube in boiling water until coagulation takes place, when it is further 
heated over the free flame and filtered. The filtrate is then tested 
with acetic acid and potassium ferrocyanide. Should no albumin 
be thus demonstrable, the entire amount of urine is treated in the 
same manner and requires no further addition of acetic acid. If, 
however, the test yields a positive result, it is apparent that the urine 
was not sufficiently acid. The entire volume is then treated with a 30 
to 50 per cent, solution of acetic acid, drop by drop, the mixture being 
thoroughly stirred and specimens being tested from time to time, as 
described. When, finally, the urine remains clear or shows only a 
faint turbidity, 100 c.c. or less, according to the amount of albumin 
present, are first heated in boiling water until the albumin begins to 
separate out in flakes, and then carefully brought to the boiling- 
point over the free flame. The supernatant urine is now decanted 



Tin: URINE. 363 

off through a filter, dried at 120° to 130° C, and accurately weighed, 
when the whole amount of the precipitate is itself brought upon the 
filter. Any albumin remaining in the beaker is detached from its 
sides by means of a small glass rod, tipped with a piece of rubber- 
tubing and collected by the aid of hot water, with which the entire 
precipitate is now thoroughly washed, until the washings no longer 
become turbid when treated with a drop of nitric acid and silver 
nitrate ; in other words, until the chlorides have been completely re- 
moved. The precipitate is further washed with alcohol and finally 
with ether to remove any fats that may be present, when it is dried 
at 120° to 130° C. until a constant weight is reached. If still greater 
accuracy be required, the dried and weighed precipitate must now 
be incinerated to determine the amount of mineral ash in combina- 
tion with the albumin, which is then deducted from the previous 
weight. The best results are obtained, if not more than 0.2 to 0.3 
gramme of albumin is contained in the amount of urine employed, 
so that a smaller quautity than 100 c.c. should be used if a pre- 
vious test with Esbach's albuminimeter shows a higher percentage. 

A glass-wool filter insures a more rapid process of drying — twenty- 
four to thirty hours ; but care must then be had that this is properly 
prepared, so as to guard against a loss of the wool while washing. 

Test for Serum-globulin and its Quantitative Estima- 
tion. To test for serum-globulin the urine is rendered alkaline by 
the addition of ammonium hydrate, any phosphates that may thus 
be thrown down being filtered off on standing. The urine is then 
treated with an equal volume of a saturated solution of ammonium 
sulphate, when the occurrence of a precipitate will indicate the pres- 
ence of the globulin. Ammonium urate, which may likewise sepa- 
rate out, can always be recognized by its color. 

If a quantitative estimation of the globulin is to be made, the pre- 
cipitate thus obtained, after about one hour's standing, is collected 
on a dried and weighed filter and washed thoroughly with a one-half 
saturated solution of ammonium sulphate until a specimen of the 
washings treated with acetic acid and potassium ferrocyanide no 
longer gives a precipitate. It is then treated as directed in the 
method employed for the quantitative estimation of serum-albumin. 

According to Paton, the following test may also be employed : 
The urine after having been rendered alkaline with sodium hydrate 
— any phosphates which may separate out being filtered off — is care- 
fully poured down the side of a test-tube containing a saturated solu- 



364 CLINICAL DIAGNOSIS. 

tion of sodium sulphate so as to form a layer above this, when in 
the presence of serum-globulin a white ring will appear at the zone 
of contact. 

Tests for Albumoses. It has been pointed out that the albu- 
moses are precipitated in the ordinary tests for serum-albumin, and 
that a precipitate referable to these bodies will clear up upon the 
application of heat, to reappear again upon cooling, and that in the 
presence of nitric acid the fluid will assume a deep yellow color. If, 
however, coagulable albumin be also present, which is usually the 
case, this should first be removed by strongly acidifying the urine 
with acetic acid, adding an equal amount of a saturated solution of 
sodium chloride and boiling. Should albumoses be present, these 
will separate out in the filtrate upon cooling. If, furthermore, the 
hot filtrate be rendered alkaline with sodium hydrate, a red color 
(biuret-reaction) will result upon the addition of a very dilute solu- 
tion of copper sulphate, added drop by drop. When boiled with 
JfiUon's reagent a red color is also obtained. This reagent is pre- 
pared by dissolving 1 part of mercury in 2 parts of nitric acid of 
a specific gravity of 1.42 and diluting with 2 volumes of water. 

Tests foe Peptones. That peptones in the sense of Kuhne do 
not occur either in normal or pathologic urines has already been 
pointed out, and the method to be described has therefore only refer- 
ence to peptone in the older sense of the word. Hofmeister's method 
is so tedious and time-consuming that the author has substituted 
Salkowski's modification, which is both accurate and simple, so 
much so in fact that its general adoption in the clinical laboratory 
can be strongly recommended. 

Fifty c.c of urine are acidified in a beaker with 5 c.c. of hydro- 
chloric acid and precipitated with phosphotungstic acid, the mixture 
being heated over the free flame, when in a few minutes the precipi- 
tate will form a resinous mass which closely adheres to the bottom 
of the vessel. The supernatant fluid is decanted off, and the mass at 
the bottom, which now becomes granular, washed twice with dis- 
tilled water, which is likewise removed by decantation. The pre- 
cipitate is then covered with about 8 c.c. of distilled water and treated 
with 0.5 c.c. of a sodium hydrate solution (sp. gr. 1.16). Upon 
shaking the beaker the mass will dissolve, the solution assuming a 
dark-blue color. This is heated on the free flame until the blue 
color turns to a dirty, grayish-yellow ; the solution at the same time 
becomes turbid, but at times may turn vellow and remain clear. 



THE URINE. 365 

This decoloration may be hastened by the further addition of a few 
drops of sodium hydrate solution. As soon as this point lias been 

reached, some of the liquid is placed in a test-tube, allowed to cool, 
and then treated with a very dilute solution of copper Bulphate ( 1 to 
2 per cent), drop by drop, when in the presence of peptones the 
solution assumes a bright-red color, which may be brought out still 
more strongly if the specimen is now filtered. If albumin or much 
mucin be present, these bodies must first be removed (see p. 362 
and below) ; but the quantity of urine employed is so small that the 
mucin can be usually disregarded. With this method, which occu- 
pies only about five minutes, 0.015 gramme of peptones pro 100 c.c. 
may be demonstrated without difficulty. 

Tests for (Mucin) Nucleo-albumin. The carefully filtered 
urine is treated in a test-tube drop by drop with an excess of con- 
centrated acetic acid, when the occurrence of a turbidity will indicate 
the presence of nucleo-albumin. 

If the urine contain albumin, this must first be removed, simple 
boiling being sufficient. Dilution of the urine should also be prac- 
tised when any doubt is felt, as urates will then not interfere with 
the reaction, nor will the urinary salts, if these be present in large 
amounts, be so apt to exert a solvent action upon the mucin. In 
order to remove mucin from the urine, it is treated with neutral 
acetate of lead, when the mucin will be carried down in the precipi- 
tate, an excess of the reagent being carefully avoided. If it is 
desired to test for peptones, the filtrate is then treated with hydro- 
chloric acid and the process continued as described above. 

Tests for Haemoglobin. The diagnosis of hemoglobinuria is 
based upon the demonstration of haemoglobin, viz., methemoglobin 
in the urine in solution, in the absence of red corpuscles, or at least 
in the presence of only a very small number, so that an examination 
in the latter direction also is an important factor. 

Bloody urine is generally turbid and may vary in color from 
bright-red to almost black. 

Oxyhemoglobin, as such, can only be recognized by the spectro- 
scope, giving rise to the appearance of two bands of absorption, 
situated between D and E, as described in the chapter on the Blood. 

The urine to be examined spectroscopically should be rendered 
feebly acid by means of acetic acid, and placed before the open slit 
of the spectroscope in a test-tube, beaker, or similar vessel, when 
the tw T o bands of oxyhemoglobin will be seen either at once or upon 



366 CLINICAL DIAGNOSIS. 

carefully diluting with distilled water. If ammonium sulphide be 
now added, the spectrum of reduced haemoglobin will be obtained. 
It must be remembered, however, that more commouly the spectrum 
of niethsemoglobin is seen in cases of hemoglobinuria. 

The following tests, which will also indicate the presence of blood 
coloring-matter, cannot be employed to decide the nature of the pig- 
ment present, as rnethsemoglobin and oxyhemoglobin will both react 
in the same manner. 

Heller's test. Some of the urine to be examined is boiled in a 
test-tube with caustic potash, when in the presence of blood coloring- 
matter the precipitate, which consists of basic phosphates, will present 
a bright-red color. At times, when the urine contains a large 
amount of coloring-matter (bile-pigment, etc.), it may be difficult to 
appreciate the color of this sediment ; in this case it should be fil- 
tered off and dissolved in acetic acid, when if blood-pigment be 
present the solution becomes red, and the color vanishes gradually 
upon exposure to the air (v. Jaksch). Instead of this test, the fol- 
lowing one may also be advantageously employed, but, in the 
author's experience, it does not surpass in delicacy that just described. 

The guaiacum test. A mixture of equal parts of tincture of guai- 
acum and oil of turpentine, which has been ozonized by exposure to 
the air, is allowed to flow carefully along the side of a test-tube upon 
the urine to be examined in such a manner as to form a distinct layer 
above the urine, when in the presence of blood-pigment a white ring 
which gradually turns to blue will be seen to form at the surface of 
contact. 

Test for Fibrin. Fibrin usually occurs in the urine in the 
form of distinct clots, the nature of which may be determined by 
thoroughly washing them with water, when they are dissolved by 
boiling in a 1 per cent, solution of soda or a 5 per cent, solution 
of hydrochloric acid. Upon cooling, this solution is then tested as 
for serum-albumin. 

Test for histon. (See p. 353.) 

Carbohydrates. 

The carbohydrates which may occur in the urine are glucose, lac- 
tose, maltose, dextrin, levulose, inosit, and animal gum. Of these, 
glucose alone will be considered in detail in the following pages, as • 
being the only one of clinical interest. 



THE URINE 367 

Glucose. The question whether sugar--t.e., glucose — can occur 
in the urine under normal conditions has been as much discussed as 
the existence of a physiologic albuminuria, and may now be defi- 
nitely answered in the affirmative. Kiilx and Moscatelli, it is true, 
were unable to demonstrate its presence even in such large quantities 
of urine as 200 liters ; the methods employed by these observers, 
however, were not sufficiently accurate, and more recent investiga- 
tions in Baumaun's laboratory leave no doubt as to the existence 
of a physiologic glycosuria. A trace of glucose is of no clinical sig- 
nificance, being demonstrable only with the most delicate methods ; 
with the tests usually employed a normal urine is apparently free 
from sugar. Nevertheless, there appears to exist a limit to the 
assimilation of glucose on the part of the body-economy, the over- 
stepping of which leads to glycosuria, termed by Claude Bernard 
" glycosurie alimentaire." 

The question now arises, Where does this limit lie? Notwith- 
standing numerous experiments made in this direction, a definite 
answer cannot as yet be given, for, while some observers have de- 
monstrated that the ingestion of 200 to 250 grammes of sugar does 
not lead to glycosuria, sugar has been found by others after the in- 
gestion of only 100 grammes, and Helfereich even claims to have 
found sugar in the urine of individuals living upon an exclusively 
vegetable diet. 

v. Jaksch states that a glycosuria following the ingestion of so 
small an amount as 100 grammes of chemically pure glucose must be 
considered as pathologic, an observation with which those of the 
author accord perfectly. A pathologic digestive glycosuria following 
the ingestion of from 100 to 150 grammes of glucose has been ob- 
served by Kraus, Ludwig, and Chvostek in cases of atrophic hepatic 
cirrhosis, pancreatic cysts, diabetes insipidus, Basedow's disease, and 
in one case of tachycardia, v. Jaksch, on the other hand, was un- 
able to find sugar, under the same conditions, in the urine of two 
cases of hyperaernia of the liver, one case of amyloid degeneration, 
and four cases of hepatic cirrhosis, of which two were of the atrophic 
and two of the hypertrophic variety. Referring to the contradictory 
results thus obtained, he regards these as accidental and thinks it 
not at all improbable that a more satisfactory classification of hepatic 
diseases than that now existing could be made on the basis of 
an artificially produced digestive glycosuria. Negative results were 
reached in cases of leukaemia, anaemia, nephritis, and tuberculosis ; 



368 CLINICAL DIAGNOSIS. 

of nervous diseases, in minor chorea, tabes, multiple sclerosis, pro- 
gressive paralysis, hemiplegia, and cerebral tumors ; while mere 
traces were found in a case of sciatica associated with fatty degener- 
ation of all organs, in one case of morphine-poisoning, and in one of 
renal tumor. Amounts of glucose large enough to be quantitatively 
determined were observed following the ingestion of 100 grammes 
in one case of cerebral atrophy simulating tumor and associated with 
renal cirrhosis, in one case of glioma of the corpus callosum, in one 
of chronic hydrocephalus, in one of cerebral syphilis, and in one of 
cerebral embolism. Definite conclusions cannot, of course, be drawn 
from so small a number of observations. It would appear, how- 
ever, that diffuse cerebral lesions referable to alcohol and syphilis 
are more likely to give rise to digestive glycosuria than more local- 
ized lesions. Finally, it should be mentioned that in diabetes melli- 
tus the sugar may also at times disappear from the urine, its elimi- 
nation being replaced, as it were, by an excessive excretion of uric 
acid or phosphates. In such cases a glycosuria may be produced 
with ease by the ingestion of 100 grammes of glucose, a point which 
may be of considerable diagnostic significance. It is also important 
to note that the exhibition of such amounts of sugar in true diabetes 
will cause an increased elimination, while this does not appear to 
occur in the other forms of glycosuria. 

Aside from the alimentary form, just considered, which may be 
produced in any healthy individual by an over-indulgence in sugars 
and starches, a transitory glycosuria, not artificially produced, is met 
with under various conditions. A transitory glycosuria, apparently 
of central origin, is thus noted in connection with lesions affecting 
the central as well as the peripheral nervous system, such as tumors 
and hemorrhages at the base of the brain, lesions of the floor of the 
fourth ventricle, cerebral and spinal meningitis, concussion of the 
brain, fracture of the cervical vertebrae, tetanus, sciatica ; following 
epileptic, hystero-epileptic, and apoplectic seizures, mental shock 
produced by railroad accidents, etc. (traumatic neuroses), mental 
strain and worry, fatigue, and anxiety. Glycosuria following epi- 
leptic aucl apoplectic attacks, however, does not appear to be so 
common as is generally believed, v. Jaksch was unable to demon- 
strate the presence of sugar in 50 recent cases of hemiplegia, and 
the author has reached only negative results in a large number of 
cases of epilepsy, with urines voided within the first few hours fol- 
lowing the seizure. 



THE URINE. 36g 

It is a well-known fact that Claude Bernard experimentally pro- 
duced a transitory glycosuria by puncturing a certain spot in the 

floor of the fourth ventricle, the supposed origin of the hepatic vaso- 
motor nerves, and it does not seem improbable that this neurotic 
form of glycosuria may be referable to some direct or reflex influence 
affecting that portion of the medulla. 

The transitory glycosuria which is occasionally observed, particu- 
larly during convalescence, in acute febrile diseases, such as typhoid 
fever, scarlatina, measles, cholera, diphtheria, influenza, and especially 
malaria, may possibly be referable to the action of ptoma'ins or 
lenkoma'ins upon this centre, and Seegen reports five cases of mala- 
ria with u diabetes " in which both conditions disappeared under the 
administration of quinine. 

A glycosuria of toxic origin has been noted in cases of poisoning 
with curare, chloral hydrate, sulphuric acid, arsenic, alcohol, carbon 
monoxide, morphine, etc., and even after simple transfusion of nor- 
mal salt-solution into the blood. Phloridzin, a glucoside obtained 
from the bark of the root of the apple tree, will likewise cause sugar 
to appear iu the urine, the glycosuria produced, however, being tem- 
porary and ceasing with the withdrawal of the drug. 

The occurrence of a transitory glycosuria under the conditions 
above mentioned, which, moreover, may be met with in almost any 
disease, while interesting from a theoretical standpoint, must, in the 
majority of instances, be regarded as a medical curiosity only, it 
being but rarely possible to draw either diagnostic, prognostic, or 
therapeutic conclusions from its existence. 

A persistent form of glycosuria is noted in connection with certain 
lesions of the brain, especially those affecting the floor of the fourth 
ventricle, and is at times of considerable diagnostic value. 

A continuous elimination of sugar is noted principally iu the com- 
plex of symptoms to which the term diabetes mellitus has been 
applied, and it is this condition to which the greatest practical and 
theoretical interest attaches. 

Diabetes mellitus is essentially a persistent form of glycosuria, 
associated with the presence of a more or less intense polyuria and a 
greatly increased elimination of all the metabolic products normally 
found in the urine, with the exception of uric acid, which is usually 
present in diminished amount. In the more advanced cases aceton- 
uria, lipuria, and lipaciduria may also exist. Diabetes, however, is not 
a persistent form of glycosuria in an absolute sense of the word, si 

24 



370 CLINICAL DIAGNOSIS. 

times may occur in the course of the disease when glucose caunot be 
demonstrated in the urine. 

The quantity of sugar excreted may be enormous, and 180 to 
360 grammes pro die may be quite frequently observed j but, 
as stated above, this quantity may diminish to zero under various 
conditions, such as the occurrence of intercurrent diseases, but 
often also without any apparent cause, and not infrequently 
in the condition which has been termed diabetic coma. Some 
cases are also at times observed in which, from beginning to 
end, mere traces are eliminated, the total amount of sugar not 
exceeding a few grammes, while the course of the disease rapidly 
tends toward a fatal termination, so that the severity of the pathologic 
process cannot be measured by the amount of sugar eliminated. A 
few years ago the author had occasion to observe a diabetic 
patient in whom for months a daily examination of the urine never 
revealed the presence of more than 5 to 10 grammes of sugar per 
diem, and where death occurred after eighteen months. 

At the same time it should be remembered that diabetes cannot 
be excluded by one or even more negative urinary examinations, and 
the value of repeating such examinations three or four hours after 
the exhibition of 100 grammes of glucose, as indicated, cannot be too 
strongly insisted upon. 

Clinicians are in the habit of determining the severity of a case, to 
a certain extent at least, by the condition of the urine under a diet 
free from starches and sugars, generally regarding those cases as the 
more serious in which the glycosuria does not disappear under a 
diet of this character, a more favorable prognosis being given if the 
sugar disappears. It should be remembered, however, that there are 
numerous exceptions to this rule which may hold good in many in- 
stances, and that a light case — i. e., one in which the sugar has dis- 
appeared under appropriate dietetic treatment — may suddenly ex- 
hibit symptoms seen only in the most severe forms, and succumb to 
one of the numerous intercurrent maladies, while apparently severe 
cases may suddenly assume the more benign type. 

It may not be out of place in this connection to say a few words 
regarding the specific gravity of the urine. While usually very high, 
varying between 1.030 and 1.060, as pointed out in the chapter on 
Specific Gravity, comparatively low figures are noted at times, such 
as 1.012, corresponding to a quantity of urine not exceeding 1000 c.c, 
and implying, of course, a greatly diminished elimination of solids. 



THE URINE. 371 

This is especially marked in those cases described by Birscbfeld, 
in which, as pointed oat in the chapter OD Inn, the resorption cl 

nitrogenous material rrom the digestive tract is below par. Poly- 
uria, a fairly constant symptom of the more common types oi dia- 
betes mellitus, is much less pronounced in Hirschfeld's form, and 
may be altogether absent, although it is true that this may occur in 
ordinary diabetes also. 

The simultaneous occurrence of glycosuria, acetouuria, lipuria, and 
lipaciduria (which see) is probably always indicative of true diabetes. 

It is, oi course, impossible to enter here into a detailed considera- 
tion of the origin of diabetes. Suffice it to say that a persistent 
glycosuria, aside from nervous influences, may be referable, on the 
one hand, to an inability on the part of the liver to transform into 
glycogen all of the sugar which is carried to this organ, or, on the 
other hand, to an inability on the part of the muscular system of 
the body to utilize all the sugar sent to it by the liver, which may 
have performed its work properly. Accordingly, we may distin- 
guish between a hepatogenic and a myogenic diabetes. As a matter 
of fact, cases are seen, usually belonging to the milder form of dia- 
betes, in which the sugar may be temporarily caused to disappear 
from the urine by muscular exercise, a point which, bearing in mind 
the deleterious effect which a continuous excessive elimination of 
solids exerts upon the kidneys, is certainly of great therapeutic in- 
terest. On the other hand, again, cases are seen, and unfortunately 
only too frequently, in which, notwithstanding a total abstinence 
from carbohydrates and a free indulgence in muscular exercise, the 
sugar does not disappear from the urine. In such cases it is per- 
missible to speak of a hepatogenic combined with a myogenic [dia- 
betes. 

Within recent years it has been shown that pancreatic disease is 
frequently associated with diabetes, and while the number of cases 
in which no pancreatic lesions were discovered is still too large to 
warrant the conclusion that disease of this organ is invariably asso- 
ciated with glycosuria, it must still be admitted that lesions of the 
pancreas are the more frequently met with in diabetes the more closely 
the organ is examined. It appears to'be certain that diabetes may be 
produced by pancreatic disease. As to the manner, however, in 
which such a result can occur we are as yet in profound ignorance. 

Hirschfeld pointed out the fact that, while in the majority of dia- 
betic patients the proteid food ingested is quite satisfactorily utilized, 



372 CLINICAL DIAGNOSIS. 

the assimilation of albumin and fats is very much below par in others, 
and particularly so in cases of diabetes associated with pancreatic 
disease. (See also Urea.) As yet, observations in this direction are 
scanty, so that a definite opinion cannot be expressed regarding the 
utility iu diagnosis of investigations similar to those of Hirschfeld. 
The author had occasion to observe a diabetic patient for some 
length of time in whom, notwithstanding that conclusions were 
reached similar to those of Hirschfeld, the existence of pancreatic 
disease could not be determined post mortem. 

Tests for Sugar. The tests for sugar usually employed in the 
clinical laboratory depend upon the following properties of sugar : 

1. It acts as a reducing agent upon certain metallic oxides, such 
as copper and bismuth, in the presence of alkalies (Fehling's, Trom- 
mer's, Bottger's, and Ny lander's tests). 

2. In the presence of yeast (saccharomyces cerevisia?) it undergoes 
fermentation, with the formation of alcohol, carbonic acid, succinic 
acid, glycerine, and a number of other bodies, such as amyl alcohol, 
etc. (fermentation test). 

3. With phenylhydrazin sugar forms an insoluble crystalline com- 
pound — phenylglucosazon. 

4. Solutions of glucose turn the plane of polarized light to the 
right, from which property glucose has also received the name dex- 
trose. 

In every case the urine should first be tested for the presence of 
albumin, which should be removed by boiling. 

Trommels test. A few c.c. of urine are strongly alkalinized in a 
test-tube with sodium hydrate solution, and then treated with a 5 
per cent, solution of sulphate of copper, added drop by drop, until 
the cupric oxide formed is no longer dissolved. The mixture is 
carefully heated, when in the presence of sugar a yellow precipitate 
of cuprous hydroxide is formed, which will gradually settle to the 
bottom as a red sediment of cuprous oxide. 

It is important to note that while sugar, unless present in mere 
traces, can readily be detected in this manner, other substances are or 
may be present in the urine, such as uric acid, kreatin and kreatinin, 
allantoiu, nucleo-albumin, milk-sugar, pyrocatechin, hydrochinon, 
and bile-pigment, which may likewise reduce cupric oxide. Fol- 
lowing the ingestion of beuzoic acid, salicylic acid, glycerine, chloral, 
etc., reducing substances also appear in the urine. These may, 
it is true, be generally disregarded, if care be taken not to boil the 



THE URINE, ;;;;; 

urine after the addition of the copper sulphate, as the precipitation 

of cuprous oxide in the presence of sugar takes place before this 
point is reached, and the result should be regarded only as positive 
if precipitation occurs in this manner. Unfortunately, however, 

the test, when thus applied, yields only negative results, or results 
which are doubtful if only mere traces of sugar are pin sent, bo thai 
it cannot be utilized, as a rule, in the study of transitory or diges- 
tive glycosuria. 

Fehling's test. This is a modification of the test just described, 
and can only be recommended with the same restrictions. 

Two solutions are employed which must be kept in separate 
bottles, the one containing 34.64 grammes of crystallized copper sul- 
phate dissolved in 500 c.c. of distilled water, and the other 173 
grammes of the tartrate of potassium and sodium and 125 grammes 
of potassium hydrate dissolved in 500 c.c. of distilled water. Equal 
parts of these two solutions, mixed in a test-tube and diluted with 
four times as much water, are boiled and a small amount of urine 
added. In the presence of sugar a precipitate of the yellow hydrox- 
ide of copper or of red cuprous oxide will be produced, care being 
taken only to warm, but not to boil the solution after the addition of 
the urine. 

Not infrequently it will be observed that upou standing, when no 
precipitation has occurred previously, the blue color of the mixture 
changes to an emerald-green, the solution at the same time becoming 
turbid. Such a phenomenon should not be referred to the presence 
of sugar, it being in all probability due to the action of other re- 
ducing substances, such as those mentioned above. 

Bottger's test with Nylander's modification. A few c.c. of urine are 
treated in the proportion of 11:1 with Almen's solution. This is 
prepared by dissolving 4 grammes of the tartrate of potassium and 
sodium, 2 grammes of the subnitrate of bismuth, and 10 grammes 
of sodium hydrate in 90 c.c. of water, heating the solution to the 
boiling-point and filtering upon cooling, when it should be kept in 
a colored-glass bottle. The mixture of urine and Almen's fluid is 
thoroughly boiled, when in the presence of sugar a grayish, dark- 
brown, and finally a black precipitate consisting of bismuthous 
oxide, Bi0 2 , or of metallic bismuth is obtained. Albumin, if pres- 
ent, must first be removed, as owing to the sulphur contained in the 
albuminous molecule alkaline sulphides could be formed upon boil- 
ing, and acting upon the bismuth give rise to the formation of black 



374 



CLINICAL DIAGNOSIS. 



sulphide of bismuth, which may be mistaken for metallic bismuth. 
Rhubarb-pigment, as well as melanin and melauogen (which see), 
and free sulphuretted hydrogen must also be absent, as misleading 
results will otherwise be obtained. 

Nylander's test, as those of Trommer and Fehling, is, however, 
not without objections, as a partial reduction of the subnitrate of 
bismuth may also be produced by other substances, such as kairin, 
tincture of eucalyptus, turpentine, and large doses of quinine. The 
author observed a urine in which Fehling's test yielded a positive 
result, and in which a blackish discoloration was observed with 
Nylander's test, but in which the fermentation-test failed completely. 
The substance producing these results was glycosuria acid. 

Fermentation-test A small piece of ordinary compressed yeast is 
shaken with some of the suspected urine and a test-tube filled with 



Fig. 94. 




Einhorn's saccharimeter. 



the mixture, to which some mercury is added. The tube is then 
inverted into a vessel containing mercury and allowed to stand in a 
warm place (22°-28° C). If sugar be present, fermentation will 
occur in the course of twelve hours, and the carbon dioxide formed 
rise to the top of the tube, gradually expelling more and more of 



PLATE IX. 




Fhenvl-Glueosazon Crystals obtained from a Diabetic Urine. 



THE URINE. 

the urine, viz., mercury, as the amount of the gas increases. It is 
easy to demonstrate that the gas thus formed is actually carbon di- 
oxide by introducing a small piece of caustic soda into the urine, 
when owing to absorption of the carbon dioxide the liquid will again 
rise in the tube. Very convenient for this purpose also are the 
saccharimetric tubes of Einhorn (Fig. 94), which arc employed ;i< 
just described, a little mercury being poured into the bent limb to 
guard against an escape of gas. As the yeast itself, however, may 
give rise to the formation of a little gas in the absence of sugar, it 
will always be well to make a control-test with normal urine ; i.e., to 
prepare a similar tube with normal urine mixed with yeast, and to 
allow this to stand at the same temperature. If a positive result be 
thus obtained, there can be no doubt as to the presence of a ferment- 
able substance in the urine, which may not be glucose, however, as 
other carbohydrates, such as lactose, maltose, and levulose, will like- 
wise undergo fermentation. Still, if large amounts of gas be ob- 
tained and if Trommer's test also yields a positive result, it will be 
fairly safe to regard the substance present as glucose. 

Phenylhydrazin test. Six to eight c.c. of urine are treated with 
two points-of-a-knifeful of phenylhydrazin hydrochlorate and 3 parts 
of acetate of sodium, and warmed until the salts have been dis- 
solved, a little water being added if necessary. The tube is then 
placed in boiling-water for twenty to thirty minutes, and then 
suddenly plunged into cold water. If sugar be present in moderate 
amounts, a bright yellow crystalline deposit will at once be thrown 
down, partly adhering to the sides of the tube. But even in the 
presence of mere traces a careful microscopic examination will reveal 
the presence of crystals of phenylglucosazon. These are highly char- 
acteristic (Plate IX.), and cannot be mistaken for any other sub- 
stance. They are seen singly or arranged in bundles and sheaves, 
composed of very delicate bright-yellow needles which are insoluble 
in water. 

This test, properly applied, is undoubtedly not only the most 
delicate, but at the same time the most reliable, as no other sub- 
stances which may be present in the urine, excepting maltose, will 
give rise to the formation of an osazon. Hence, whenever any doubt 
is felt as to the nature of a substance reacting in a positive manner 
with the reagents described above, recourse should be had to this 
test. It has been stated that maltose forms an exception ; this, how- 
ever, will never become embarrassing, as the microscopic appearance 



3 7 '3 CLIXICAL DIAGNOSIS. 

of maltosazon crystals differs from that of the phenylglueosazon. 
The inelting-point of phenylglueosazon, ii'J'j : C. moreover, is about 
16° higher than that of the maltosazon— 190 c -l 91 : C. To deter- 
mine this point it is necessary to filter off the osazon. and. after wash- 
ing with water, to dissolve it upon a filter by means of a little hot 
alcohol. From this alcoholic solution it is reprecipitated by water. 
when it may be collected and dried over sulphuric acid. The melt- 
ing-point is then determined according to the usual meth; Is, 

Polarimetric test. Glucose turns the plane of polarized light to 
the right, but the same may be said of maltose, the degree of polar- 
ization of which is even more intense, so that it may be impossible 
to state in a siven case whether such rotation is referable to a large 
quantity of glucose or to a smaller quantity of maltose. The latter 
substance, however, occurs in the urine but rarely, and may be recog- 
nized not only by the microscopic appearance of its osazon, bat also 
by the fact that its power of reduction is increased in the presence of 
sulphuric acid and by the application of heat. 

An error which may further arise with the employment of the 
polarimetric method is referable to the fact that if glucose be present 
in only small amounts, while the urine contains large quantities of 
.5-oxybutyric acid, the latter turning the plane of polarized light 
to the left, it may happen that the rotation in this direction will neu- 
tralize or even overcome any rotation to the right due to glucose. 
In such cases, however, the urine will react in a positive manner 
with the other reagents described, and the fermented urine " 
moreover, turn the plane of polarization still more strongly to the 
left, indicating the presence of a dextro-rotat-: ■: y substance, and in 
all probability of glucose. 

The delicacy of this method varies considerably with the instru- 
ment employed: the figures given Mow were obtained with the 
apparatus of Lippich, which yields the best results. 

(For a description of this method see the Quantitative Estima- 
tion of Sugar by Means of the Polarimeter.) 

Table showing the Delicacy of the Te-ts Bescbibed. 



Tromnier"s test . 
Fehliug's test 
Nylander's test . 
Fermentation test 
Phenylhydrazin test 
Polarimetric test 



_"- per cent. 

_" 
:- " 

"- :■: 
.:_■- : 



THE URINE. 



377 



Table showing the Behavior of the Various Forms of Sugab 
which may Occur in the Urine toward phe Tests Des< ribed. 



Trommer's, viz., Xylander's Fennenta- 
Fehling's test test. tion-test. 



Phenylhydrazin 
test. 



Glucose, Positive reaction 



Positive 

reaction. 



Levulose, Positive reaction. Positive 
reaction. 



Maltose, Positive reaction. Positive 
reaction. 



Lactose, Positive reaction. Positive 
reaction. 



Positive Positive reaction ; 

reaction, melting-point 
205° 0. 

Positive Same osazon ob- 
reaction. tained as with 
glucose, only 
more rapidly. 

Positive | A maltosazon is 
reaction. formed ; melting- 
point 190-191° C. 



Laiose, 



Positive reaction; 
on boiling onlv 
1.2-1.8 per cent, 
more is obtain- 
ed than by the 
polarimeter. 



Positive 
reaction. 



No re- 
action, or 
only a 
very faint 
one. 



No re- 
action. 



No reaction in the 
concentration in 
which it may oc- 
cur in the urine ; 
melting-point, 
200° C. 

With phenylhy- 
drazin a yellow- 
ish-brown, non- 
crystallizable oil 
is obtained. 



Polarimetric 
test. 



Rotation toward 
the right. 



Flotation toward 
the left. 



Rotation toward 
the right. 



Rotation toward the 
right ; increased 
by boiling with a 
2-5 per et. solu- 
tin of sulphuric 
acid. 

No reaction or ro- 
tation toward the 
left. 



Clinically, it is unimportant to search for minute traces of sugar, 
such as may be fouud in every normal urine, aud the reader is re- 
ferred to special works ou physiologic chemistry for a consideration 
of the methods generally employed. 

Quantitative Estimation of Sugar. The methods used in the 
quantitative estimation of sugar are essentially based upon the quali- 
tative tests described. 

Fehling's method. Fehling's solution, prepared as described 
above, is of such strength that the copper contained in 10 c.c. is 
completely reduced by 0.05 gramme of glucose. If then urine is care- 
fully added to this quantity until complete reduction takes place, the 
amount of sugar contained in a given specimen of urine can be 
readily calculated according to the following equation : 

y :0.05 :: 100 : x, aud x = 5 , 

y 

in which y indicates the number of c.c. of urine required to reduce 
the 10 c.c. of Fehling's solution, and x the amount of sugar con- 
tained in 100 c.c. of urine. 

As the best results are only obtained if from 5 to 10 c.c of urine 
are used in one titration, it is usually necessary to dilute the urine to 
the required degree, in the determination of which the specific gravity 
may serve as a guide. As a general rule, urines of a specific gravity of 
1.030 should be diluted five times, and if the density be still higher, 



378 



CLIXICAL LI A GXOSIS. 



ten times. To be certain that the proper degree of dilation has been 
med, 5 c.c. of Fehling's solution are treated with 1 c.c. of the 
diluted urine, a little caustic soda and distilled water being added 
nafce in all about 25 c.c. This mixture is thoroughly boiled, and 
if the fluid still remains blue another 1 c.c. of diluted urine added, 
and so on until the last two tests differ by 1 c.c. of urine, the last 
c.c. added causing a separation of cuprous oxide. In this manner 
the percentage of sugar may be approximately determined. Albu- 
min, if present, must first be removed by boiling. 

Ten <:.o. of Fehling's solution, diluted with 40 c.c. of water, are 
placed in a p jrcelain dish and b oiled. While boiling, the diluted urine 
is added from a burette. J c.c. at a time. when, as a rule, the precipitated 
cuprous oxide will rapidly settle, so that gradually a white bottom 
may be sem through the blue fluid, the color of which becomes less and 
less intense upon the further addition of urine until, finally, the solu- 
tion is almi >st colorless. When this point is reached the urine is added 
only drop by drop, until the deoolorization is complete. The degree 
of dilution multiplied by 5 and the result divided by the number of c.c. 
of diluted urine employed will then indicate the percentage-amount 
of sugar. In the following table the percentage-results corresponding 
e number of c.c. of undiluted urine employed will be found : 

Sugar.— Quantity of glucose pre liter, corresponding tc the number of cubic 

centimeters used for the complete reduction of 10 centimeters of Fehling's 
solution.. 



- 






50.00 


45 44 


25.00 




16.66 


16.00 


12.50 


12.18 


10.00 


9.80 




- U 


7.14 


7.04 




6.16 


5.54 


5 . ; 


5.00 


4.94 


4.54 




4.16 


4.14 


3.S4 


3. SO 


3.56 


3.54 


3.32 


: -:: 


3.12 


3.10 


2.94 


. _ 






2.62 


2 62 


2.50 


2.50 


- ffl 


- 


2.26 


2.26 


2.16 


. 


. I; 


_ • 


2.00 


1.98 


1.92 


1.92 


: si 




l " ; 


1.76 


1.72 


1.70 


1.66 


1.66 



40- 

15.62 
11.90 
9.60 

- 

i 

i H 
5 -.. 
i . 
i -. 

4.12 

: n 

3 52 

: a 

3 08 

2.90 

2.60 
2.4B 

2.34 
" __ 
2JL4 

- 
198 

100 

: -. 

1.74 
1.70 
1.65 



38.46 

15.14 
1L62 

9.42 
7.92 

z.~ 

z ;. 

5.36 

4 :s 

3.76 
3.48 
3.26 
3.04 

- - 

2.60 

2 34 

2.24 
2.14 
2.06 

I..-: 

: o 
:.*: 
1.74 
L70 
1.64 



20.84 
14.15 
11.36 

9.24 

7.s: 

z ": 
5.94 
5.30 

4,7* 
4.38 
4.04 
3.74 
3.46 
3.24 
3.04 
. 9E 

. -; 

258 

2.44 
2.32 
2.22 
2.12 

: :e 
:o: 
: ss 
L8a 
: n 

170 

: o 



33.32 

_: ;•: 

11.10 



:.o 

5.24 

40: 
4^4 

-. .:■: 

3.70 
3.44 
3.22 
3.02 

. n 

2.56 

2.42 
2.32 
2.22 
2.12 

■2. A 

:..-• 

1.85 

:.*: 

104 



31.24 
19.22 
13.88 

::.-: 

- -. 

7.56 

: z z 

■:,s: 

5.20 
4.70 

e- 
■i - 

3.42 
3.20 

so-: 

: -_: 
. -:: 

2.20 

2.12 
2.04 
1.94 

1.85 
1 91 
1.74 



1 _ 1.62 



i- "•: 

13.50 

:: z. 

8.76 
7.44 

■: ^ 

5.16 

4." 
4.26 
3.96 

r.'z 

3.40 
3.18 

_ - 

2.64 
2.54 
2.40 

: ;. 

2.20 
2.10 

1.94 

l.z-z 

:.*:■ 

1.74 

0:2 



27.76 
13.14 

:: 4: 

? -:: 
-.:-- 

z -.. 

:.:8 
5.12 
4.62 
4.1. 
3.92 
3.62 
i 
3.16 
2.96 

_o: 

2.64 

2.40 

--- 

. :s 

2.10 

:.:■: 

1.92 

: -: 
:.s: 

L74 

l.Or 



: : • : 

13 24 

ii'.s: 
:: :■: 

S.v 

6.32 
5.60 
5.06 
4.58 

4..: 

E.-:-" 
3.34 
3.14 

_ r4 

2.64 

i.e.; 

:.--- 

2.10 
2.02 

: v. 

1.8: 
l.SJ 
1.72 
L66 

:o: 



THE URINE. 379 

Unfortunately, it is difficult as a general rule to determine ex- 
actly the point when all the copper has been reduced ; /.,., the poinl 
at which the blue color has entirely disappeared. When it is thought 
that this has been reached, about 1 c.c. should be filtered through thick 

Swedish filter-paper, and the filtrate, which must be absolutely clear, 
acidified with acetic acid and treated with a drop or two of a solu- 
tion of potassium ferrocyanide. If unreduced copper be still present 
in the solution, a brown color will result, indicating that insufficient 
urine has been added. But if, on the other hand, no brown dis- 
coloration be noted, it is possible that the desired point has already 
been passed, when the titration should be repeated. At times the 
precipitate will not settle at all, aud even pass through the filter, so 
that it is almost impossible to determine the end of the reaction. In 
such cases the following procedure, suggested by Cause, will be found 
serviceable : 

Ten c.c. of Fehling's solution are diluted with 20 c.c. of distilled 
water aud treated with 4 c.c. of a -^ per cent, solution of potassium 
ferrocyanide. While boiling, the diluted urine is now added drop 
by drop, until the blue color has entirely disappeared, a precipitate 
not appearing at all with this method. 

In order to obtain reliable results, however, the Fehling's solu- 
tion must be prepared with great care, and its strength deter- 
mined. This may be done in the following manner : 0.2375 gramme 
of crystallized cane-sugar, pure and dried at 100° C, is dissolved 
in 40 c.c. of distilled water to which 22 drops of a y 1 ^- per cent, 
solution of sulphuric acid have been added. This solution is kept 
upon a boiling water-bath for an hour, when it is allowed to cool 
and diluted to 100 c.c. with distilled water. Twenty c.c. of this 
solution will then contain exactly 0.05 gramme of glucose, corre- 
sponding to 10 c.c. of Fehling's solution, if this be of the required 
strength. If too strong, so that 21 c.c, for example, of the sugar 
solution are required to obtain a complete reduction of the copper, 
the strength of Fehling's solution may be determined according to 
the equation : 20 : 0.05 : : 21: x, and x = 0.0525. If too weak, on 
the other hand, so that 19 c.c, for example, are required, its strength 
is similarly determined : 20 : 0.05 : : 19 : x, and x = 0.0475. If 
necessary, the solution may of course be brought to the exact strength 
in the manner indicated elsewhere, by first making it too strong 
and then ascertaining the required degree of dilution. 

Differential density method. This method is very useful in el in i- 



380 



CLINICAL DIAGNOSIS. 



Fig 



cal work and should be preferred to the more uncertain titration 
with Fehliug's solution, unless considerable experience has been ac- 
quired with this method. 

The specific gravity of the urine is accurately ascertained by means 
of a pyknometer, or a hydrometer accurately graduated to four deci- 
mals and provided with a thermometer indicating tenths of a degree. 
The temperature at which the specific gravity is taken should be 
that for which the hydrometer has been constructed, the urine being 
heated and cooled to the desired degree. 100 to 200 c.c. are then 
set aside in a flask, after the addition of some yeast which has been 
washed free from mineral material, loosely stoppered or provided 
with an arrangement like the one shown in the accompanying figure 

(Fig. 95). After twenty-four hours, if 
but little sugar be present, or forty-eight 
hours, if there be much, the specific gravity 
is again determined under the precautious 
given after having filtered the urine. 
The difference in the specific gravity is 
then multiplied by 230, an empirical fac- 
tor which has been found by dividing the 
amount of sugar ascertained by titration 
or polarization with the difference in the 
density of the urine after fermentation, the 
result indicating the percentage of sugar. 
The process may be hastened if to every 
100 c.c. of urine, 2 grammes of tartrate 
of potassium and sodium and 2 grammes 
of diacid-sodium phosphate be added with 
10 grammes of compressed yeast, and the 
mixture allowed to stand at a temperature of from 30° to 34° C. 
If but little sugar be present, two to three hours will be sufficient. 

That portion of the urine in which the specific gravity is deter- 
mined before fermentation should really be treated in the same man- 
ner. It will suffice, however, to add 0.022 to the specific gravity 
found, to make up for the increase that should otherwise be observed 
in the second specimen owing to the addition of the salts. 

In every case the urine must be perfectly fresh, as fermentation 
will generally begin spontaneously even after standing a short time. 
Einhom's method. This will answer very well for ordinary pur- 
poses. Two especially constructed and graduated sacchari metric 




Flask for the approximate esti 
mation of sugar by fermentation 
(v. Jaksch.) 



THE URINE. 



381 



tubes (Fig. 94) are used, one of which is filled with a mixture of the 
suspected urine and yeast, the other with normal urine and peast, 
as a control. The tubes are then set aside at a temperature ol From 
30° to 34° C, when the percentage-amount oi sugar in the urine is 
read off from the column of the carbon dioxide present. Should the 
second tube also show a small amount ol' gas, the figure correspond- 
ing to this amount is deducted from the first. 



Fig. 96. 




Soleil-Ventzke's saccharimeter. 



Polarimetric method. For this purpose the saccharimeter of 
Soleil-Ventzke is very convenient (Fig. 96). This consists essen- 
tially of a Nicol's prism, a, which may be rotated about the axis 
of the apparatus ; a second Nicol's prism at d ; vertically placed 
compensating prisms, consisting of dextro-rotatory quartz at e, 
which may be moved horizontally by means of a rack-and-pinion 
adjustment, this being turned by a milled head at /;, so that 
light can pass through a thicker or thinner layer of the dextro- 
rotatory quartz. At / there is a plate of gyro-rotatory quartz cut 
perpendicularly to the optical axis, covering the entire field of 
vision; at h biquartz plates of Soleil, and at i an Iceland-spar 
crystal ; b c represents a small telescope, by means of which 
the biquartz plates can be accurately focussed. When the compen- 
sation-prisms of this apparatus are in a certain position, the gyro-rota- 
tion of the plate / will be exactly compensated and the two halves 



382 CLINICAL DIAGNOSIS. 

of the field of vision present the same color, while the zero of the 
scale x will coincide with the zero of the vernier y, arranged on 
the upper surface of the compensators. Any change in this position 
produced by turning the screw h will cause the appearance of a 
different color in each half of the field of vision. If now, with 
a zero-position, an optically active dextro- or gyro-rotatory substance 
be interposed, the color of each half of the field of vision will be- 
come altered, but may be equalized again by changing the position of 
the compensators, the degree of change necessary to produce this 
result constituting an index of the power of rotation of the solution 
interposed in the tube m. 

Soleil-Ventzke's apparatus is constructed in such a manner that if 
a solution of glucose be employed, the length of the tube m being 
10 cm., every entire line of division on the scale will indicate 1 per 
cent, of sugar. 

The tube of the saccharimeter should be carefully washed out 
with distilled water, and at least once or twice with the filtered 
urine, when it is placed on end upon a flat surface, and filled with 
the urine to such a degree that this forms a convex cup at the end. 
The little glass plate is now carefully adjusted, so as to guard against 
the admission of bubbles of air. The metallic cap is then placed in 
position, care being taken to avoid undue pressure. The examina- 
tions are made in a dark room, an ordinary lamp being used, and 
several readings taken, until the differences do not amount to more 
than one-tenth or two-tenths per cent. The tubes should be thor- 
oughly cleansed immediately after the experiment. 

In every case the filtered urine should be free from albumin, and, 
if markedly colored, previously treated with neutral acetate of lead in 
substance and filtered. 

If it be desired to demonstrate only the presence of sugar, the 
compensators are first brought to the zero-position. If now, upon 
the interposition of the tube filled with urine, a difference in the 
color of the two halves of the field of vision be noted, the presence of 
an optically active substance in the urine may be assumed, and if at 
the same time the deviation be to the right, the presence of glucose 
is rendered highly probable, while a deviation to the left will gener- 
ally be referable to levulose or oxybutyric acid. Indican, peptones, 
cholesterin, and certain alkaloids, it is true, also turn the plane of 
polarization to the left, but as a rule these substances need not be 
considered, cholesterin occurring but rarely, while indican in dia- 



THE URINE. 

betic urines is usually present in only small amounts, and a con- 
currence oi' sugar and peptones has not as yet been observed. Lac- 
tose and maltose, which also turn the plane of polarization to the 
right, maybe distinguished from each other and from glucose by the 
phenylhydrazin test. Levulose tnms the plane oi polarization to 
the left. Oxybutyria acid is practically always associated with the 
presence of glucose, and may be recognized by allowing the mine to 
undergo fermentation, when the filtered urine will become distinctly 
gyro-rotatory. 

Comparatively little interest, from a clinical point of view, at- 
taches to the occurrence of other forms of sugar in the urine. 

Lactose. Lactose may be found in the urine near the end of 
gestation, but more especially in nnrsing-women in whom the flow of 
milk is impeded, owing to the existence of mastitis, for example. 
It has also been stated that lactosuria occurs in nursing-women who 
have well-developed breasts, in the absence of any obstruction, and 
that the good qualities of a wet-nurse are indicated by a copious and 
persistent elimination of milk-sugar. Its presence may be inferred 
if a positive result is obtained with Trommer's and Nylander's tests, 
while the phenylhydrazin and fermentation tests give negative results. 

Levulose. Levulose is occasionally found in diabetic urines 
together with glucose, its presence being often indicated by the fact 
that a polari metric examination shows a deviation to the left or none 
at all, while the other tests for sugar indicate the presence of a re- 
ducing substance. 

Maltose. Maltose together with glucose was found in the urine 
of a patient supposedly the subject of pancreatic disease, asso- 
ciated with an acholic condition of the stools. Its recognition is 
practically dependent upon the formation of its osazon and a deter- 
mination of the melting-point of this. 

Dextrin. In one case of diabetes dextrin appeared to take the 
place of glucose. It may be recognized by the fact that upon the 
application of Fehling's test the blue liquid first becomes green, 
then yellow and sometimes dark brown. 

Laiose. Laiose occurs at times in the urine of diabetic patients. 
It is essentially characterized by the fact that by titration with 
Fehling's solution from 1.2 to 1.8 per cent, more sugar is indicated 
than by the polari metric method. 

Animal gum. Animal gum, according to modern researches, 
is a constant constituent of normal urine, but of no clinical inter 



384 CLINICAL DIAGNOSIS. 

Inosit. Inosit does not occur normally in the urine, but may be 
demonstrated after the ingestion of large amounts of water. Patho- 
logically it has been demonstrated in cases of diabetes insipidus and 
in albuminuria, but is of no especial interest. 

Urinary Pigments and Chromogens. 

In considering the subject of urinary pigments it is necessary to 
differentiate sharply between such pigments as occur preformed in 
the urine and others that only appear upon the addition of certain 
reagents which have the power of decomposing their chromogens. 
Until quite recently this subject was in a most confused condition, 
and even now our knowledge can only be regarded as rudimentary; 
for, notwithstanding the fact that numerous investigations have 
been made with a view to determine the source of the color of normal 
urine, this problem even is not as yet definitely solved, and it is only 
possible to say at the present time that urochrome and possibly a 
certain indoxyl derivative are to some extent responsible for the 
normal color of the urine. 

Under normal conditions urochrome and uroerythrin, to which 
latter the red color of urate sediments is due, are the only known 
pigments occurring preformed in the urine, while indigo-red and 
indigo-blue, derived from indoxyl sulphate and indoxyl glycuro- 
nate, may be artificially produced. Pathologically, on the other 
hand, various other pigments may be found, occurring in the urine 
either free or in the form of chromogens. Among the former 
there may be mentioned haemoglobin, methaamoglobin, haamatin, 
hsematoporphyrin, urorubrohsematin, urofuscohaamatin, urobilin, the 
biliary pigments and melanin, while abnormal chromogens are seen 
following the ingestion of certain drugs, such as santonin, senna, 
rheum, iodine, etc., as also in cases of poisoning with carbolic acid, 
creosote, etc. The occurrence of some of these substances, such as 
that of the various forms of blood-pigment, of the biliary pigments, 
and indigo, viz., indican, is of considerable clinical interest, while 
others again are only of minor importance. 

Normal Pigments. Urochrome. Tc the presence of this pig- 
ment, which appears to be identical with the normal urobilin oj 
MacMunn, but which should not be confounded with the patho- 
logic urobilin of Jaffe, the normal yellow color of the urine appears 
to be due to a certain extent. It is undoubtedly derived from 
bilirubin, which in turn is referable to the hsematin and haemoglobin 



THE URINE. 

of the blood and results from the bilirubin scented into the intes- 
tinal tract by a process of oxidation, and not of reduction, as 18 
generally stated. Such a transformation, according to our present 

knowledge, may, however, also occur directly, without the interven- 
tion of bilirubin, as urochrome is found in the urine of dogs in 
which the bile is preveuted from entering the intestinal tract by the 
establishment of a biliary fistula. An increased amount is simi- 
larly found iu cases in which resorption of large extravasations of 
blood is taking place in the body — in short, whenever an increased de- 
struction of red corpuscles is noted; while under the opposite circum- 
stances — i.e., in conditions associated with a definite formation of red 
corpuscles, as in certain forms of anaemia, chronic parenchymatous 
nephritis, diabetes, diseases of the bone-marrow, etc. — it occurs in 
diminished amount. 

In order to obtain urochrome from normal urine, this is acidu- 
lated with 1-2 grammes pro liter of dilute sulphuric acid, filtered, and 
saturated w 7 ith ammonium sulphate in substance, when the flakes 
which are found in an excess of the salt are dried and treated with 
warm slightly ammoniacal absolute alcohol, the pigment being ob- 
tained upon evaporation of the alcohol. An alcoholic solution of 
urochrome, like the urobilin of Jarfe, exhibits a beautiful greenish 
fluorescence when treated with ammonia and a few drops of a solu- 
tion of zinc chloride, but unlike the latter substance its acidulated 
alcoholic solutions present a broad band of absorption at " F," ex- 
tending more to the left than to the right of this Hue, while the 
remainder of the spectrum at the same time is absorbed to the right 
end from a point somewhat to the left of "6." 

Uroerythrin. Uroerythrin is the pigment which imparts the red 
color to crystals of uric acid and urate sediments. Iu pathologic 
conditions it is seen especially in cases of hepatic insufficiency, in 
which the Jiver, owing to a greatly increased destruction of red cor- 
puscles, is either unable to transform all the blood-pigment which is 
carried to it into bile-pigment, and also where an absolute insuffici- 
ency on the part of the hepatic cells exists, so that the organ is not 
even capable of causing the transformation of a normal amount of 
haemoglobin. Uroerythrin is thus seen in notable quantities in cases 
of pneumonia, malarial fever, erysipelas, spinal curvature, hepatic 
cirrhosis, carcinoma of the liver, etc. Chemically its close relation 
to haemoglobin, haematoidin, and bilirubin is seen from the following 
analyses of the various pigments : 

25 



386 CLINICAL DIAGNOSIS. 



c 


H 


N 





S 


Fe 


[semoglobin, 53.85 


7.32 


16.17 


. . . . 


0.39 


0.43 


[asmatoidm, 65.05 


6.37 


9.51 








ilirubin, 67.83 


6.29 

5.79 


9.79 


16.79 






•roerrtlirm. 62.51 


31. 


70 





When present in large amounts uroerythrin is readily recognized 
by the salinon-red color which it imparts to urinary sediments. 
Otherwise it is best to precipitate the uriDe with neutral acetate of 
lead, barium chloride, or a similar reagent, when in the absence of 
uroerythrin a milky-white precipitate is obtained, a pale rose- 
colored sediment indicating the presence of the pigment in appreciable 
amounts, a more pronounced rose-color being produced by large 
quantities. In every case at least ten to fifteen minutes should be 
allowed to elapse before forming a definite conclusion, so that the 
sediment may have abundant time to settle. 

Normal Chromog-ens. The chromogens occurring in normal 
urine are indican, uroha^matin, and an unknown chromogen which 
yields urorosein when treated with mineral acids. 

Indican. It has already been pointed out (see Sulphates) that the 
indol formed during the process of intestinal putrefaction is oxi- 
dized to indoxyl in the blood ; this, entering into combination 
with sulphuric acid, is eliminated in the urine as sodium, viz., 
potassium indoxyl-sulphate, or indican, as represented by the equa- 
tions : 

I. C 5 H T X - O = C s H T XO. 
Indol. Indoxyl. 

OH C 8 H 6 NO 

n. CH-XO -f SO,' =SO,/ -H,0. 

" x OH "\OH 

Indoxyl. Indoxyl-sulphate. 

XsHeNO /C s H 6 XO 

III. SO,' -XaoHP0 4 = SOo< -XaH,P0 4 . 

" x OH * x OXa 

Indoxyl-sulphate. Indoxyl-sodium sulphate. 

Formerly it was thought that indican was also formed within the 
tissues of the body in the absence of putrefactive organisms (this 
view having been held especially by Salkowski). Further re- 
searches, however, have demonstrated beyond a doubt that micro- 
organisms are always concerned in the production of indican, and 
that in health the large intestine is its only source. Thus, Baumaun, 
who succeeded in absolutely disinfecting the intestinal tract in a dog 
by meaus of large doses of calomel, observed that all traces of indi- 



THE URINE. 

can, as also of phenol and paracresol, disappeared from the urine 

According to Senator, moreover, indican docs not occur in the urine 
of newly born infants which have not as yet received nourishment. 
This observation is a strong point in favor oi Nencki's teachings thai 

indol is a specific product oi' albuminous putrefaction in the pres- 
ence of organized ferments, as putrefiable substances arc present, 
but no putrefactive organisms. Tuczek's observations on absti- 
nence from food in cases of insanity, in which indican was only 
observed in the urine when albumins, even in minimal amounts, 
were ingested, also speak very strongly against Salkowski's theories. 
Finally, it has been demonstrated that in cases in which an arti- 
fical anus is established near the distal end of the ileum the con- 
jugate sulphates disappear almost entirely from the urine, while they 
reappear in normal amount as soon as the connection between the 
small and large intestines has been re-established. 

The amouut of indican normally eliminated in the urine varies 
somewhat with the character of the diet, Jaffe having found 6.6 
milligrammes in 1000 c.c. of urine as an average of eight observa- 
tions. The largest quantities excreted in health are found after a 
liberal indulgence in animal food, particularly the so-called red 
meats, while the smallest amounts are observed during a milk or 
kefir diet. By means of the latter article, indeed, the greatest 
diminution in the degree of intestinal putrefaction may be effected 
in man. In pathologic conditions an increased elimination of indican 
is observed : 

1. In all cases associated with an increased degree of intestinal 
putrefaction. As there appears to be little doubt that this is largely 
regulated by the acidity of the gastric juice, an increased indican- 
uria, according to personal observations, is encountered when ana- 
chlorhydry or hyperchlorhydry exists. It has been pointed out else- 
where that it is possible to form a fairly accurate idea of the amount 
of free hydrochloric acid in the gastric juice by an examination of the 
urine in this direction. Very large quantities of indican are thus 
eliminated in cases of carcinoma of the stomach, and exceeded only 
by those observed in cases of ileus, so that this symptom in the 
author's estimation is one of considerable value in differential diag- 
nosis, and one, moreover, which has not as yet received the attention 
which it undoubtedly deserves. Exceptions to this rule are at times, 
though rarely, met with, for which it is, however, impossible to account 
definitely at the present time. Large quantities of indican arc further 



388 CLINICAL DIAGNOSIS. 

observed in cases of acute, subacute, and chronic gastritis, of what- 
ever origin. In the course of personal observations in this direction 
the author was struck with the curious phenomenon that in cases of 
ulcer of the stomach, uotwithstanding the simultaneous occurrence of 
hyperchlorhydry, an increased elimination of indican, contrary to 
what is usually seen in hyperchlorhydry, referable to other causes, is 
quite constantly found. Possibly the existence of muscular atony 
noted in those cases may serve to explain this apparent incongruity, 
but it is as yet impossible to offer a satisfactory explanation of the 
phenomenon. Remembering the origin of indican, and the relation 
which the amount eliminated bears to the degree of intestinal putre- 
faction, it will be unnecessary to enumerate the long list of diseases 
in which an increased indican uria has been observed, as it will be 
found that in the majority of these cases the indicanuria is merely 
an index of the condition of the gastric juice. 

2. It should be noted that in cases in which the peristaltic move- 
ments of the small intestine have become impeded, as in ileus, acute 
and chronic peritonitis, an increased elimination of indican will in- 
variably take place, no matter what the state of the gastric juice 
may be. In such conditions, indeed, and especially in ileus, the largest 
quantities are observed, a point which may be of decided value in 
differential diagnosis, as diseases of the large intestine alone are never 
associated with an increase in the amount of indican. In simple, un- 
complicated constipation increased indicanuria is not seen, and should 
an examination in such cases reveal the presence of more indican 
than normal, it will be safe to assume the existence of disease else- 
where, especially of the stomach. 

3. As albuminous putrefaction can also take place within the 
body, an increased indicanuria is observed in cases of empyema, put- 
rid bronchitis, gangrene of the lungs, etc. ; but while in the condi- 
tions mentioned above the indol-producing organisms appear to be 
especially active, the elimination of phenol in the latter condition 
may be more pronounced at times than that of indican. Bearing in 
mind the points here set forth the author cannot agree with others in 
saying that the study of indicanuria possesses no importance from a 
clinical standpoint ; he maintains, on the other hand, that an ex- 
amination of the urine in this direction is at least as important as the 
testing for albumin and sugar, and that points of decided importance, 
not only in diagnosis, but also in prognosis and treatment, can thus 
be gained. 



THE URINE. 389 

When indican is treated with hydrochloric acid it is decomposed 
into sulphuric acid and indoxyl ; should an oxidizing Bubstanoe 
be present at the same time, indigo-blue, the blue coloring-matter oi 
the urine, results : 

2C 8 H 6 NK30 4 + 20 = C 16 H 10 N 2 O, + 2IIKSO,. 
Potassium indoxyl- Indigo-blue, 

sulphate. 

Indigo-blue in small amounts may be found free in the sedi- 
ment oi almost every decomposing urine, usually occurring in the 
form of small amorphous granules, and more rarely in crystalline 
form. Urines have been observed which were blue when passed, 
or which turned blue, as a whole, upon standing. Such a phenome- 
non must, however, be regarded as a medical curiosity. The blue pig- 
ment which may be obtained from urines has been variously de- 
scribed as Prussian-blue, urocyanin, cyauourin, Harnblau, uroglaucin, 
choleraic urocyanin, but has been ultimately shown to be indigo-blue, 
derived from a colorless mother-substance present in every urine to 
a greater or less extent, which has been named indican, and which 
has been shown to be identical with the uroxanthin of Heller and 
Thudichum's choleraic urocyaninogen. 

Test for indican. Unfortunately the methods which so far have 
been proposed for the purpose of quantitatively determining the 
amount of indican in the urine are not only inaccurate, excepting, 
perhaps, the spectroscopic method devised by Miiller, but, what is 
more, are too lengthy and complicated to be of value to the practising 
physician. As a consequence the observations made by almost all 
observers are based upon an approximative estimation only. For 
practical purposes such a method, particularly the one to be pres- 
ently described, is sufficient, the degree of increase which interests us, 
of course, more particularly being judged fairly accurately thereby, 
as is quite generally admitted by those who have employed this 
method, and have compared the same with the results obtained with 
the more complicated ones mentioned. 

The most convenient method is a modification of that of Jaffe, sug- 
gested by Stokvis : 

The urine of twenty-four hours is carefully collected and a spc. i- 
men taken for examination. A few c.c. of urine are mixed with an 
equal amount of concentrated hydrochloric acid, and 2 or o drops <>1 
a strong solution of sodium hypochlorite, calcium hypochlorite, or 
common saltpeter, and 1-2 c.c. of chloroform added. The mixture 



390 CLINICAL DIAGNOSIS. 

is thoroughly agitated and set aside. The indigo which has been set 
free in this manner is taken up by the chloroform, coloring this blue 
to a greater or less extent, the degree of increase as compared with 
the normal being determined by the intensity of the color. Albumin 
need not be removed. Bile-pigment, which interferes with the re- 
action, is removed by means of a solution of subacetate of lead care- 
fully added in order to avoid an excess. Urines presenting a very 
dark color may be cleared in the same manner. Potassium iodide, 
which, if present, will, owing to the liberation of free iodine, color 
the chloroform more or less of a carmine, must also be removed. For 
the sake of comparison, it is well to employ the same quantities of 
urine and reagents in every case, marked tubes being very convenient 
for this purpose. 

In this connection it may be said that the author has found this 
method to be at the same time a fairly sensitive test for albumin, 
the mixture of hydrochloric acid and urine upon the addition of the 
oxidizing agent preseuting a well-marked cloudiness on the surface 
of the liquid, which gradually extends downward. 

Urohcematin. Uroh&ematin appears to be the chromogen of the 
red pigment of the urine, and is very likely closely related to in- 
doxyl. Very little, however, is known of its chemical composition 
or, indeed, of its mode of formation. In all probability the red pig- 
ment which may be obtained from this substance is identical with 
other red pigments which have been described from time to time as 
occurring in the urine, such as that of Scherer, the urrhodin of Heller, 
the urorubin of Plosz, Schunk's indirubin, Bayer's indigo-purpurin, 
Giacosa's pigment, and also the indigo-red obtained by Rosenbach 
and Rosin by careful oxidation of the urine with nitric acid. 

Further investigations are necessary before this subject is fully 
understood, but bearing in mind the probable origin of urohsematin 
from indoxyl, it would possibly be best to speak of the red pigment 
as indigo- red. 

The presence of urohsematin in normal urine — i.e., a chromogen 
yielding a red pigment when treated with certain reagents — may 
be demonstrated by shaking urine with chloroform and decanting 
after several days, when the addition of a drop of hydrochloric acid 
to the chloroform extract will cause the appearance of a beautiful 
rose color, varying in intensity according to the amount of the 
chromogen present. 

In accordance with the view that uroha3matin is an indoxyl deriv- 



THE URINE. :;<H 

ative, its clinical significance is similar to that of indican (which 
see). The purplish color so often obtained in the chloroform ei 
tract, when Stokvis's modification of Jaffa's indican test is employed, 

is due to a mixture oi' indigo-blue and indigo-red. Indican, 
however, always appears to be present in larger amounts than nro- 
hsematin ; and in normal and usually also in pathologic urines a red 
color is not obtained with the test mentioned. In a few isolated 
cases of ileus, peritonitis, and carcinoma oi' the stomach the author 
found more indigo-red than indigo-blue. 

The so-called " Reaction of Rosenbach " is a convenient test for in- 
digo-red when this is present in increased amounts : the boiling mine 
is treated drop by drop with concentrated nitric acid, when in the 
presence of large amounts of indigo-red it will assume a dark Bur- 
gundy color, which sometimes takes on a bluish tinge if held to the 
light. Owing to a precipitation of the pigment the mixture at the 
same time becomes cloudy, the foam assuming a blue color. In 
well-marked cases the Burgundy color does not appear to be changed 
by the further addition of nitric acid, but will sometimes, when 
10-20 drops of the acid have been added, suddenly turn from red 
to yellow. This reaction Rosenbach regarded as a most constant 
symptom of various forms of severe intestinal disease associated with 
an impeded resorption throughout the entire intestinal tract. Ewald 
likewise noted this reaction in cases of extensive disease of the small 
intestine, in carcinoma of the stomach, acute and chronic peritonitis, 
but obtained negative results in carcinoma of the colon, stricture of 
the oesophagus, chronic diarrhoea, etc. Rosenbach's reaction should 
be viewed in the same light as a highly increased elimination of in- 
dican ; the author has met with the same in all conditions associated 
with greatly increased intestinal putrefaction, and, as did Ewald, failed 
to note the reaction in a few cases of occlusion of the large intestine, 
in which an increased elimination of indican is likewise uever observed. 

Uroroseinogen. In addition to indican and urohaematin still 
another chromogen, which yields a rose-red pigment when treated 
with mineral acids, appears to occur in normal urine, although in 
small amounts. Beyond the fact that the chromogen is no conju- 
gate sulphate, practically nothing is known of its chemical nature. 
The pigment, which has received the name uroroscin, or Harnrosa, 
appears to be identical with Heller's urophain. Urorosein may best 
be demonstrated by treating 5-10 c.c. of urine with an equal amount 
of concentrated hydrochloric acid and 1 or 2 drops of a concent rated 



392 CLINICAL DIAGNOSIS. 

solution of bleaching-powder, when in the presence of much indican 
the mixture first assumes a dark greenish, blackish, or dark-blue 
color, owing to the formation of indigo. When the mixture is 
shaken with chloroform the supernatant fluid will exhibit a beautiful 
rose color, due to the urorosein. This may then be extracted with 
amyl alcohol and separated from any other pigment present at the 
same time by shaking with sodium hydrate, whereby the solution 
is decolorized. Upon the addition of a drop or two of hydro- 
chloric acid to the alcoholic extract the rose color will reappear. 
Such solutions, however, soon become decolorized upon standing. 
A rose-red ring, referable to this pigment, is also frequently ob- 
tained in pathologic urines when the ordinary nitric-acid test is 
employed. 

While normally urorosein can only be obtained in traces, appreci- 
able amounts are often met with in pathologic conditions associ- 
ated with grave disturbances of nutrition, as in nephritis, diabetes, 
carcinoma, and dilatation of the stomach, pernicious anaemia, typhoid 
fever, phthisis, and at times in profound chlorosis, etc. A vegetable 
diet also appears to cause an increase in the amount of the chromogen. 

Pathologic Pigments and Chromogens. The blood-pigments. 
The blood-pigments proper which may occur in the urine have al- 
ready been considered (see p. 366), and in this connection it will 
only be necessary to refer briefly to the occasional presence of hsern- 
atin, urorubrohaBtnatin, urofuscohsematin, and haBmatoporphyrin. 

Hcematin is only rarely seen. In order to demonstrate its presence 
the urine is rendered strongly alkaline with ammonia, filtered, and 
the filtrate examined spectroscopically, when the spectrum shown in 
Fig. 6 will be noted, which may be changed into the spectrum repre- 
sented in Fig. 7 by the addition of ammonium sulphide. 

Urorubrohcematin and urofuscohcematin are two pigments which 
were observed by Baumstark in the urine of a case of pemphigus 
leprosus complicated with visceral lepra, and which appear to be 
closely related to hsernatin. The color of the urine in this case varied 
between dark red and brownish-red, strongly suggesting the pres- 
ence of blood. In order to separate out the pigments the urine was 
dialyzed and the contents of the dialyzer dissolved in sodium hy- 
drate solution. Upon the addition of hydrochloric acid to this solu- 
tion a brown pigment separated out in flakes, while a second pigment 
remained in solution, imparting to it a beautiful red color. Upon 
filtration the acid filtrate was again subjected to dialysis, when the 



THE URINE. 393 

red pigment likewise separated out. The former Bubetance Baum- 
stark termed urorubrohsematin, and the latter urofuscohamatin. 

UrohamcUoporphyrin has the formula (VJI^NJ ) ; , and is prob- 
ably closely related to the hsematoporphyrin resulting from the 
action of sulphuric acid upon hsematin. MacMunn found a pig- 
ment answering the description of this substance in the urine in 
cases of rheumatism, Addison's disease, pericarditis, and paroxysmal 
hemoglobinuria, which he termed urohsematin, but which in all 
probability was hsematoporphyrin. Le Nobel found the same 
pigment in two cases of hepatic cirrhosis and in one case of croupous 
pneumonia. More recently hsematoporphyrin has been repeatedly 
noted in the urine during a long-continued administration of sul- 
phonal. Clinically its occurrence does not appear to be of any special 
significance. Urines rich in hsematoporphyrin present an abnormal 
color, varying from a sherry or port-wine tint to Bordeaux. Al- 
bumin in uncomplicated cases is not present, and hsematoporphyrin 
itself does not give the albumin reaction. In urines presenting the 
color just described hsematoporphyrin may be tested for in the fol- 
lowing manner : 

Thirty c.c. of urine are treated with an alkaline solution of barium 
chloride. The precipitate, after having been washed with water, and 
then with absolute alcohol, is extracted with ordinary alcohol acidu- 
lated with hydrochloric acid, by rubbing in a mortar. The solution 
thus obtained will present a reddish color in the presence of hsema- 
toporphyrin, and its filtrate yield the characteristic spectrum of the 
latter substance; i. e., four bands of absorption, of which two are 
broad and dark and two light and narrow. The former alone are 
characteristic, and frequently the only ones visible. One of these 
extends beyoud " D " into the red portion of the spectrum, while the 
other is situated between " b " and " F." Of the other two bands. 
oue may be seen between u C" and " D," and the other between 
u D " and " E," nearer « E " (Fig. 9). 

In conclusion it may be said that a chromogen of hsematoporphy- 
rin also usually occurs in urines containing the free pigment, which 
probably explains why such urines gradually become darker on 
standing. 

Biliary pigments. Of the four biliary pigments, viz., bilirubin, 
biliverdin, biliprasin, and bilifuscin, the former alone is met with in 
freshly voided urines, while the others may form upon standing, 
being oxidation-products of bilirubin. As this pigment is never round 



394 CLINICAL DIAGNOSIS. 

in normal urines, its occurrence may be regarded as an infallible 
symptom of disease. 

In health it will be remembered that bilirubin, C 16 H 18 N 2 3 , formed 
in the liver from blood-pigment, is eliminated into the small intestine, 
in which it is transformed into hydro-bilirubin and largely excreted 
as such in the feces, while a small portion is resorbed into the 
blood and eliminated in the urine as urochrome, or normal urobilin. 
Whenever then the outflow of bile into the intestines becomes im- 
peded bilirubin is absorbed by the lymphatics and eliminated in the 
urine, icterus at the same time resulting. 

Among the numerous causes which can give rise to eholuria under 
such conditions may be mentioned obstruction of the biliary ducts 
and especially of the common duct, referable to simple swelling of 
its mucous membrane, as in the ordinary forms of catarrhal jaun- 
dice ; it may also be due to the presence of a biliary calculus, to 
parasites, compressiou of ihe duct by tumors of the liver, the gall- 
bladder, the duct itself, and of neighboring structures, particularly 
the pancreas, stomach, and omentum. Whenever the blood-pres- 
sure in the liver is lowered, so that the tension iu the smaller biliary 
ducts becomes greater than that in the veins, eholuria likewise re- 
sults. The icterus occurring under these conditions has been termed 
hepatogenic icterus, in contradistinction to the form observed in cases 
in which the liver has either totally or partially lost the power of 
forming bile, owing to the existence of degenerative processes affect- 
ing its glandular epithelium, as in cases of acute yellow atrophy, or 
in which the destruction of red corpuscles is going on so rapidly and so 
extensively that the organ is incapable of transforming into biliru- 
bin all the blood-pigment which is carried to it. This occurs in cases 
of pernicious ansemia, malarial intoxication, typhoid fever, in poison- 
ing with arseniuretted hydrogen, etc. The icterus neonatorum is 
probably to a certain extent also dependent upon the latter cause. 
To this form the term hematogenic icterus has been applied. In 
such cases the occurrence of bilirubin in the urine can ouly be ex- 
plained by assuming that a transformation of blood coloring-matter 
into bilirubin has taken place in the blood itself or in other tis- 
sues of the body. As a matter of fact, it appears to be quite gener- 
ally accepted that such a transformation can actually occur outside 
of the liver, as the hsematoidin which may be found in old extrava- 
sations of blood seems to be identical with bilirubin. On the other 
hand, however, the existence of a hsematogenic icterus is positively 



THE URINE. 

denied, especially by Stadelmann. In accordance with his view it 
may actually be demonstrated that in cases of pernicious anaemia, 
malaria, etc., the urine does not contain bilirubin, but usually uro- 
bilin. In cases of this kind which the author had occasion to ex- 
amine bilirubin was never found. Further investigations are Qi 
sary to settle this question definitely. 

Usually the presence of biliary pigment may be recognized by 
ocular inspection, as urines which contain this in notable amounts 
present a color varying from a bright yellow to a greenish-brown. 
Any morphologic elements which may occur in the sediment art- 
stained a golden-yellow, and the same color is imparted to the foam 
of the urine, as well as to the filter-paper used in its filtration. At 
times, however, and particularly in cases in which the icterus is only 
beginning to appear, the presence of bilirubin is not infrequently 
overlooked, and urines containing urobilin in large amounts may be 
similarly mistaken for icteric urines. In doubtful cases, therefore, 
whether icterus exists or not, but in which the urine presents an 
intense yellow color, it is necessary to have recourse to chemical tests. 
A large number of these have been devised for the purpose of de- 
monstrating the presence of bilirubin, all of which are fairly reliable. 
Only those will be described here which the author has had occa- 
sion to employ personally and which deserve especial consideration 
as being the most delicate : 

Smith's test, as modified by Rosin : 5-10 c.c. of urine are placed in 
a test-tube and treated with 2 or 3 c.c. of tincture of iodine which has 
been diluted with alcohol in the proportion of 1 : 10, in such a manner 
that the iodine solution forms a layer above the urine. In the pres- 
ence of bilirubin a distinct emerald-green ring will be seen to form at 
the zone of contact. This test can be highly recommended as being 
the simplest, and is not surpassed in delicacy by any other. 

Huppert's test: 10-20 c.c. of urine are precipitated with milk of 
lime (a solution of barium chloride is, perhaps, still more conven- 
ient), and the precipitate, after filtering, brought iuto a beaker by 
perforating the filter and washing its contents into the latter with a 
small amount of alcohol acidulated with sulphuric acid. The mix- 
ture is boiled, when in the presence of bilirubin the solution assumes 
a bright emerald-green color. Huppert's test is as delicate as that 
of Smith, but not so convenient for the needs of the practising 
physician. 



396 CLINICAL DIAGNOSIS. 

Gmelin's test, as modified by Rosenbach : The urine is filtered 
through thick Swedish filter-paper, when the latter is removed and 
a drop of concentrated nitric acid, which has been allowed to stand 
exposed to the air for a short time, is placed upon its inner surface. 
In the presence of bilirubin rings presenting the colors of the rain- 
bow will be seen to form around the nitric acid. 

Gmelin's test : The urine is treated with nitric acid, which is car- 
ried to the bottom of the test-tube by means of a pipette, so as to 
form a layer beneath the urine, when a color-play, as already de- 
scribed (p. 354), will take place at the line of contact between the two 
fluids, the green color being the most marked. 

In this connection a few words may also be said of the occurrence 
in the urine of biliary acids and cholesterin. 

Biliary acids. These may be demonstrated in the urine whenever 
bile-pigment is present, so that their clinical significance is essentially 
the same as that attaching to bilirubin. Their demonstration is, 
however, attended with such difficulties that the methods devised for 
this purpose may well be omitted here (see also p. 173). 

Cholesterin. Cholesterin has never been found in icteric urines 
and is only rarely seen in other pathologic conditions. It has been 
observed in cases of chyluria, fatty degeneration of the kidneys, dia- 
betes, in one case of epilepsy, and in two cases of pregnancy, v. 
Jaksch has noted the presence of cholesterin crystals in a urinary 
sediment in a case of tabes and cystitis. The author found choles- 
terin crystals in the sediment in a case of acute nephritis. The urine 
was of a dark-amber color, cloudy, of an acid reaction, and a specific 
gravity of 1.028. In the sediment numerous hyaline and epithelial 
casts and some red blood -corpuscles were found. Giiterbock de- 
scribed a urinary calculus obtained from the bladder of a woman which 
consisted almost entirely of cholesterin (see also Feces). 

Beginners at times regard the spangles of urea nitrate seen in urines 
rich in urea, after the addition of nitric acid, as cholesterin, an error 
which should be guarded against. 

Pathologic urobilin. This pigment should not be confounded with 
the urochrome or normal urobilin described above, to which it is 
closely related, but from which it may be readily distinguished by 
means of the spectroscope. Gautier states that pathologic urobilin 
may be obtained from urochrome by submitting the latter to the ac- 
tion of reducing agents. Like normal urobilin it is derived from 
the coloring-matter of the blood and bilirubin, merely representing a 



THE URINE, 397 

lower form of oxidation than normal urobilin, It is said to be 
identical with the stercobilin found in the Vc<vs. While its occur- 
rence in the urine is essentially a pathologic phenomenon, it is at 
times also met with in normal urines, and appears to he derived 
from a special chromogen, urobilinogen, from which it may he set 
free by the addition of an acid. From its frequent occurrence in 
febrile urines pathologic urobilin has also received the name febrile 
urobilin. It is, however, also observed in many other condi- 
tions, and especially in cases presenting the so-called hematogenic 
form of icterus, from which fact, indeed, and the usual absence <>)' 
bilirubin at the same time, this form has also been termed " urobilin 
icterus." In this connection it is interesting to note that, according 
to v. Jaksch, bilirubin occurs in the blood in almost every case in 
which urobilin is preseut in the urine, showing that bile-pigment 
circulating in the blood is in all probability transformed into urobi- 
lin in the kidneys. 

Urobilinuria has been observed in certain hepatic diseases ; in 
twelve cases of atrophic and hypertrophic cirrhosis examined v. 
Jaksch was able to demonstrate the preseuce of urobilin in the urine 
in every instance, a point which at times may be of considerable 
diagnostic importance, providing that other causes which are known 
to lead to urobilinuria can be eliminated. The author has observed 
urobilin in a few cases of hepatic cirrhosis, chronic malaria, and per- 
nicous anaemia, in all of which the skin presented a light icteric hue, 
and in which bile-pigment was absent from the urine. An examina- 
tion of the blood was, however, unfortunately not made. Urobilin 
has also been noted in cases of carcinoma, scurvy, Addison's disease, 
haemophilia, retrouterine hsematocele, extrauterine pregnancy, fol- 
lowing intracranial hemorrhages, etc. 

Urines which are rich in urobilin usually present a dark-yellow 
color, strongly suggestive of the presence of bilirubin ; the foam even 
jn such cases may be colored, making the resemblance between the 
two pigments still more complete, v. Jaksch further points out 
that urines containing indican in large amounts often likewise pre- 
sent a very dark-yellow color, a statement with which personal ob- 
servations are in perfect accord. It is possible that the color in 
such cases may be due to the presence of humiu-substances derived 
from the indican. In every case a more detailed chemical examina- 
tion should hence be made. The method suggested by v. Jaksch 
appears to be more serviceable than that suggested by Gerhardt. 



398 CLINICAL DIAGNOSIS. 

v. Jakseh's test. 10-20 c.c. of urine are submitted to Huppert's 
test (which see), when in the presence of urobilin in notable quanti- 
ties the precipitate assumes a brownish-red color, which disappears 
upon boiling with ac'dulated alcohol, the liquid at the same time 
becoming colored a brownish or pomegranate-red. In the pres- 
ence of only a small amount of the pigment, on the other hand, the 
liquid is colored only a light reddish tinge. 

Gerhardfs test. If the urine contains much urobilin, which the 
color will indicate, 10-20 c.c. are extracted with chloroform by 
shaking, and the extract treated with a few drops of a dilute solution 
of iodo-potassic iodide. Upon the further addition of a dilute solu- 
tion of sodium hydrate the chloroform extract is colored a yellow or 
yellowish-brown and exhibits a beautiful green fluorescence which 
is even more intense than that noted in the case of normal urobilin. 

At times, however, all tests fail and recourse must then be had to 
the spectroscope. In acid solutions urobilin presents a distinct band 
of absorption between "b" and " F," extending beyond "F" to 
the right, while in alkaline solutions a band is likewise seen between 
i( b" and "F," which does not extend beyond " F," however, and is 
less intense. 

Jlelanin and melanogen. In cases of melanotic disease it has been 
repeatedly observed that the urine, which usually and probably al- 
ways presents a normal yellow color when voided, gradually becomes 
darker upon exposure to the air, finally turning black. This phe- 
nomenon indicates without doubt that such urines contain a chro- 
mogen, melanogen, which, upon oxidation, yields the black pigment 
noted in these cases, viz., melanin. As yet it has not been possible 
to isolate this substance in crystalline form, and it is, indeed, not defi- 
nitely determined that the black color in such urines is referable to 
one single pigment. Such urines generally contain melanin and its 
chromogen in solution; deposits of melanin granules by themselves 
are only occasionally seen, and are not at all characteristic, as they 
may also be found in cases of chronic malarial intoxication, etc., when 
they may, indeed, be met with in the blood, constituting the condi- 
tion spoken of as melanoemia. 

"While" \he occurrence of melanin in the urine is probably indica- 
tive, in most cases, of the existence of melanotic tumors, it should 
be stated that this symptom cannot be regarded as pathognomonic, 
as it may be absent in the case of melanotic tumors and pres- 
ent in wasting diseases and inflammatory affections, and may at 



THE URINE, 

times, though very rarely, even be associated with the presence 
of non-pigraented growths. Nevertheless, its occurrence should 
always be regarded with suspicion, and, taken in conjunction with 
other symptoms, will often lead to a correct diagnosis. 

Urines which darken upon standing should be subjected to the 
following tests : 

1. A few c.c. of urine are treated with bromine-water, when in 
the presence of melanin or melanogen a precipitate will be obtained 
which is yellow at first and then gradually turns black. 

2. The addition to melanotic urine of a few drops oi a strong solu- 
tion of perchloride of iron will cause the appearance of a gray color. 
which is imparted to the precipitateof phosphates occurring at the time 
if more of the reagent be added, and which dissolves again in au excess. 

Phenol urines. The development of a dark brown or black color 
in urines upon standing is not always due to the presence of melanin, 
as the same appearance may be noted in cases of poisoning witli 
carbolic acid, following the ingestion of salol, hydrochinon, pyro- 
catechin, and salicylic acid, etc., in large doses. The color in such 
cases is due in all probability to the presence of various oxidation- 
products of hydrochinon, and in the last instance possibly to the so- 
called humin-substances. 

The test referred to above will prevent any confusion as to the ori- 
gin of the color noted, as far as melanin is concerned, and with the 
history of the case given, moreover, further chemical examination will 
generally be unnecessary. In suspected cases of carbolic-acid poison- 
ing, however, the mineral as well as the conjugate sulphates should be 

A 

quantitatively determined, when the factor — (see Sulphates) will be 

found to be greatly diminished. If at the same time other factors 
which might cause a greatly increased elimination of conjugate sul- 
phates can be excluded, the diagnosis of poisoning with carbolic acid, 
or one of its derivatives, may be inferred. Salol and salicylic acid 
may be recognized from the fact that such urines when treated with 
a solution of perchloride of iron develop a marked violet color which 
does not disappear on standing. The reaction thus differs from 
that obtained with diacetic acid. 

Alkapton. Urines are at times, though very rarely, seen which, 
as those just described, also turn dark on standing, while present- 
ing a normal color when voided. A chemical examination will show, 
however, that in these cases melanin as well as hydrochinon and its 



400 CLINICAL LIAGXOSIS. 

derivatives is absent. The source of the color in such urines has 

been referred to the presence of an aromatic oxyacid. which has been 
variously termed glyeosurie acid, uroleucinic acid, urrhodinic acid, 
but which is more commonly spoken of as alkapton. The term alkap- 
tonuria, however, is frequently applied to the presence of related 
oxyaeids in the urine as well, snch as para-oxyphenyl acetic acid, 
hydro-para-cumaric acid, para-oxyphenylglycolic acid, uxyamygdalic 
acid, and homogentisinic acid. Glyeosurie acid is more frequently 
seen in children than in adults, its presence being apparently due to 
some such metabolic anomaly as the occurrence of eystin and dia- 
mines iu the urine, the condition at times occurring in families, aud 
persisting for years. Although it has been found in pathologic con- 
ditions, viz.. in phthisis, and in one case of brain-tumor, no connec- 
tion appears to exist between any local lesion and the alkaptonuria. 
Marshall, who was the first to obtain glyeosurie acid in a pure form, 
noted a ^raduallv increasing weakness in his case. 

The presence of such acids may at times give rise to confusion, and 
a case of alkaptonuria may be mistaken for one of glycosuria, if reli- 
ance be placed only upon Fehling's or Trommer's test for sugar. 
Several years ago the author had occasion to examine a urine con- 
taining glyeosurie acid, the following note having been made at the 
time : " The urine presents a dark-brown color, which has developed 
on standing. Its reaction is acid : the specific gravity 1.028. It 
reduces Fehling's solution, but does not reduce the subnitrate of 
bismuth, causing merely a blackish discoloration : the fermentation- 
test is negative. When Ehrlich's test is applied, a dark-brown color 
develops on standing for fifteen minutes, while at the end of an hour 
the urine has turned almost black. 

Tor methods of isolating glyeosurie acid, see Neobauer and Vogel's 
Urinary Analysis. 

Blue urines. Blue urines are sometimes seen, the blue color being 
due to indigo formed from urinary indican. in all probability, within 
the urinary passages. Their occurrence can be regarded only as a 
medical curiosity. Formerly, when indigo was employed in the 
treatment of epilepsy, blue urines were frequently seen. At the 
present time, when methylene-blue is occasionally used in the treat- 
ment of malaria and chyluria, the pigment is found in the urine. 

Green urines. Green urines have also been described, the cause 
of the color of which, however, has not been definitely ascertained. 

Pigments referable to drugs. Certain drugs may also cause changes 



PLATE X. 



Ehrlich's Diazo-Reaction, as modified by the author. The orange color 
in the lower portion of the test tube may be obtained in any urine; the 
dark carmine ring indicates the presence of the reaction in a well-pro- 
nounced degree; the colorless zone above is intended to indicate the 
ammonia that has been added. 



THE UR1NR 4()1 

in the normal color of urine, and in doubtful cases inquiry in this 
direction should be made. It has been pointed out that carbolic 
acid, hydrochinon, pyrocatechin, and said will cause the appearance 

of a dark-brown color, and that after the administration oi indigo and 
methylene-blue blue urines are voided. Santonin, rheum, and senna, 
furthermore, color urines a bright yellow, so that they may resemble 
icteric urines in appearance. The yellow color in such eases is 
changed to an iutense red by the addition of an alkali, and if am- 
nion iacal fermentation be going on at the same time in the bladder 
the patieut may suppose himself to be suffering from hematuria. 
The red color thus produced is due to the action of the alkali upon 
chrysophanic acid. When urines containing copaiba are treated 
with hydrochloric acid a red color results which changes to violet 
upon the application of heat. During the administration of potas- 
sium iodide, or the use of iodine in any form, a dark mahogany color 
is obtained when the urine is treated with nitric acid. In doubtful 
cases Stokvis's modification of Jaffe's test for indican should be em- 
ployed, when in the presence of an iodide the chloroform assumes a 
beautiful rose-red color. 

For the detection of other drugs and poisons in the urine the 
reader is referred to special works. 

EhrlicWs reaction. In pathologic conditions, and particularly in 
typhoid fever, a chromogen appears to be present in the urine, which,, 
when treated with a solution of diazo-benzeue-sulphonic acid and am- 
monia, imparts a color to the urine which varies from eosin to a deep 
garnet-red (Plate X.). This reaction, which is generally spoken of as 
Ehrlich's reaction, or the "diazo reaction/' was for a time regarded as 
pathognomonic of typhoid fever. Subsequent researches have shown, 
however, that it is also at times met with in other acute febrile diseases, 
such as scarlatina, measles, malaria, smallpox, pneumonia, etc., and 
notably in phthisis pulmonalis, in which it is frequently observed, and 
in which its presence for any length of time may be regarded as a bad 
omen. Still there appears to be no doubt that its occurrence in doubt- 
ful cases may be regarded as pointing to typhoid fever, especially when 
found between the fifth and the thirteenth day of the disease, and when 
it disappears later on. The author has studied this question in a large 
number of instances, and has arrived at the conclusion that while the 
reaction may be observed in other diseases as well as in typhoid fever, 
it is usually not difficult to distinguish between those and the latter 
condition, excepting certain cases of acute miliary tuberculosis. Afi 

26 



402 CLINICAL DIAGNOSIS. 

the reaction, however, is obtained not later than the twenty-second 
day of the disease, and is usually present as early as the filth or sixth 
day in typhoid fever, and while it generally does not appear earlier 
than the beginning of the third week and then persists almost to 
the end in acute tuberculosis, its occurrence may be of decided value 
in diagnosis in many instances. 

Its absence from the fifth to the ninth day in typhoid fever usually 
indicates a very mild case, excepting in children. This rule, how- 
ever, is not an invariable one. The author recently observed a case 
of typhoid fever in which, notwithstanding exceedingly high tem- 
peratures (106.5° F.), the reaction was not obtained before the be- 
ginning of the third week, and then persisted for only a few days. 

The author cannot agree with v. Jaksch when he states that he 
" disclaims for this test any clinical importance whatsoever, and that 
he would enjoin the necessity of avoiding inferences based upon the 
appearance of the reaction indicated." Xor does he believe that 
" the color, when obtained, is always due to acetone, and that the 
diazo reaction is rather an uncertain indication of that body than a 
test for anything else/' as he has not only been unable to demonstrate 
this reaction in a large number of cases of diabetes in which acetone 
was present, but has likewise only occasionally observed acetone in 
cases of typhoid fever in which a positive result was obtained, not- 
withstanding a most careful examination. As v. Jaksch, however, 
in his text-book, does not speak of the addition of ammonia, which is 
just as important as the addition of the diazo-compound, the negative 
results obtained by others may possibly be owing to this error. The 
author had occasion repeatedly to observe that physicians who had 
applied this test according to v. Jaksch's faulty directions, with nega- 
tive or doubtful results, changed their opinion materially as to the 
value of the reaction when correctly instructed. 

Since the preparation of chemically pure, crystalline diazo-com- 
pouuds is a difficult process, Ehrlich made use of the fact that sul- 
phanilic acid when treated with nitrous acid in a nascent state 
forms diazo-benzene-sulphonic acid, which thus becomes the active 
principle in the mixture employed. 

Other compounds, of course, can also be used, as the meta-amido- 
benzene-sulphonic acid, the ortho-and para-toluidine-sulphonic acids, 
etc., but of all these Ehrlich found the common sulphanilic acid the 
most convenient. Two solutions kept in separate bottles are em- 
ployed, the one containing 50 c.c. of hydrochloric acid, which is 



THE URINE. .{(,;> 

diluted to 1000 c.c. and saturated with Bulphanilic acid, the other 
being a 0.5 per cent, solution oi sodium nitrite 

To make the test, 40 c.c. of the sulphanilic acid solution are taken 
in a measuring-glass, and 1 c.c. oi the sodium nitrite solution added, 
the mixture being thoroughly shaken. The hydrochloric acid ads 
upon the sodium nitrite, forming nitrous acid, which, in a nascent 
state, forms the diazo-benzene-sulphonic acid by its action upon the 
sulphanilic acid. Small quantities of the sodium nitrite are used, the 
absence of any free nitrous acid in the mixture being thus insured ; 
very small quantities of the diazo-benzene-sulphonic acid are at the 
same time formed, one of the principal requirements in order to in- 
sure success iu the experiment. 

The reaction which takes place is represented as follows : 

I. NaN0 2 + HC1 = NaCl + HN0 2 . 

.NH 2 N ^ 

II. C 6 H,( + HN0 2 =C 6 H 4 ( 5N + 2H 2 0. 

X S0 3 H \S0 3 / 

Para-amido-benzene-sul phonic Diazo-benzene-sulphonic 
acid. acid. 

In his original article Ehrlich advises the addition of this mixture 
in the proportion of 1 : 1 per volume to the urine to be tested. If 
ammonia be added in excess to the urine thus treated, the color- 
play presently to be described occurs. In a later communication 
(Char itS Annalen, 1886, Bd. 11) he has modified this method by 
mixing 1 volume of urine with from 5 to 6 volumes of absolute 
alcohol previous to the addition of the sulphanilic-acid mixture, 
filtering, and then adding the acid mixture to the filtrate. 

It is convenient to add about 50 c.c. of absolute alcohol to 10 c.c. 
of urine, to filter, and then to add to the alcoholic urine, which has 
become more or less decolorized, the sulphanilic-acid mixture from 
a burette ; 20 c.c. of the latter added to about 30 c.c. of the alcoholic 
urine are sufficient. The addition of the acid in small quantities, 
2 c.c. at a time, for example, followed by thorough shaking of the 
urine, is at times useful, especially in typhoid fever, when the disease 
has advanced to a point at which the color-reaction has no longer its 
original intensity. By the addition of a few drops of ammonia to the 
final mixture the characteristic color appears in typhoidal urine; this, 
however, disappears on shaking, and becomes permanent only after an 
excess of ammonia has been added. A small Erlenmeyer's flask 
is more convenient for holding the urine than the ordinary test-tuhe, 



404 CLINICAL DIAGNOSIS. 

the exact shade being more apparent by transmitted light. With this 
modified method most of the author's experiments were performed. 

There is a third method, however, which is more convenient, less 
expensive, and more delicate. A few c.c. of urine are poured into a 
small test-tube, when an equal quantity of the sulphanilic-acid mix- 
ture is added, the whole being thoroughly shaken ; 1 c.c. of ammonia 
is then allowed to run carefully down the side of the tube, forming 
a colorless zone above the yellow urine containing the acid. At the 
junction of the two a more or less deeply colored ring will be seen, 
the color of which is readily distinguished, the slightest carmine 
tinge being shown more readily by contrast with the colorless zone 
above and the yellow below, than when dealing with a uniform color. 
If the mixture be then poured into a porcelain basin containing water, 
a salmon-red color will be obtained if the reaction be positive, while a 
yellow or orange color is obtained when negative. This latter addi- 
tional test the author has found most valuable in doubtful cases. 

As to the color-play which takes place in different urines, it will 
be observed that in normal, or pathologic, but non-febrile urines, 
the color of the pure, or alcoholic, urines, when method No. 2 is 
employed, remains either unaffected or is merely intensified by the 
addition of the ammonia. A deep orange tint may even be produced 
in this way, but is of no significance whatsoever, and is easily dis- 
tinguished from the typical color. Ehrlich records one exception to 
this rule, namely, that in urines containing biliary coloring-matter 
an intensely dark, cloudy discoloration occurs at times, which, upon 
boiling, is changed to an intense reddish-violet color. 

In the course of certain experiments auother very interesting ex- 
ception was met with, but it is to be regretted that there is only one 
observation to record, which the author owes to the kindness of Dr. 
Ogden, of Milwaukee. The urine in this case contained a substance 
which reduced Fehling's solution, but did not reduce the subnitrate 
of bismuth, producing merely a black discoloration ; the fermenta- 
tion-test failed completely. Undoubtedly this was one of the rare 
instances in which glycosuric acid, first isolated by Marshall (see 
above), occurred in the uriue. When Ehrlich^s test was applied 
to this urine according to the second method a dark-brown color 
developed on standing for fifteen minutes, which at the end of an 
hour turned almost to black. As regards febrile urines, Ehrlich 
observed an intensely yolk-yellow color, which was even imparted 
to the foam when method No. 1 was employed, in rare instances of 



THE URINE, j,.;, 

endocarditis ulcerosa, abscessus hepatis, and intermittens ; /'.'., in dis- 
eases associated with well-marked chills. 
In typhoid fever,and this is most important, a color varying from 

eosin to a deep garnet develops upon the addition of ammonia. I [ere 
method Xo. 2, and particularly No. 3, were found very useful, as 
with these the production of the faintest rose-tinl is more readily 
perceived than when Xo. 1 is employed, owing to the fact that in 
the second method we are practically dealing with a primarily color- 
less solution, and in Xo. 3, as above stated, we can take; advantage 
of contrasts. 

Conjugate Sulphates. In addition to indoxyl (see Indican); 
skatoxyl, phenol, paracresol, and pyrocatechiu occur in the urine in 
combination with sulphuric acid. 

Skatoxyl. Skatoxyl results from the skatol formed during the 
process of intestinal putrefaction, as indoxyl is derived from indol, 
and is partly eliminated in the urine as skatoxyl sulphate. Clini- 
cally it is of little interest, as the amount excreted is very small, and 
it will not be necessary here to enter into a further consideration of 
its chemical properties or modes of detection (see Feces). 

Phenol. Phenol, according to the researches of Brieger, occurs 
in only small amounts in human urine, the phenol reactions being 
largely caused by paracresol. Xormally only about 0.03 gramme is 
eliminated in the tweuty-four hours, but in pathologic conditions 
much larger quantities may be found. These conditions are essen- 
tially the same as those described under Indicanuria, but it should 
be remembered that while an increased elimination of indican is usu- 
ally associated with an increased elimination of phenol, a dimin- 
ished excretion of the former, in those cases in which the increased 
degree of intestinal putrefaction is referable to disease of the stom- 
ach, is never, so far as personal observations go, associated with an 
increased elimination of phenol. In cases, however, in which an 
increased elimination of conjugate sulphates is due to albuminous 
putrefaction going on in other parts of the body, as in cases of 
empyema, pulmonary gangrene, putrid bronchitis, etc., an increased 
elimination of phenol alone may be noted, the amount of indican 
being about normal. A greatly increased excretion of conjugate sul- 
phates referable to phenol alone is especially observed in cases of 
poisoning with carbolic acid or one of its derivatives (see also Indi- 
canuria and Sulphates). 



406 CLINICAL DIAGNOSIS. 

The method employed for the demonstration of phenol in the urine 
is the same as that used in its quantitative estimation : 

Principle : When potassium-phenyl sulphate is treated with 
hydrochloric acid phenyl sulphate results, which further takes up one 
molecule of water, giving rise to the formation of sulphuric acid and 
phenol, according to the following equations : 

/O.C 6 H 5 /O.C 6 H 5 

I. S0 2 < + HC1 = KC1 + S0 2 ( 

x OK x OH. 

/O.C 6 H 5 .OH 

II. S0 2 ( + H 2 = S0 2 < + C 6 H 5 .OH. 

X OH ^OH 

By the action of bromine-water upon phenol a yellowish-white 

crystalline precipitate of tribromophenol is formed: 

C 6 H 5 .OH + 6Br = 3HBr + C 6 H 2 Br 3 .OH. 

As 331 (molecular weight) parts by weight of tribromophenol cor- 
respond to 94 (molecular weight) parts by weight of phenol, the 
amount of the latter contained in a certain volume of urine is readily 
determined according to the equation : 

331 : 94 :: x : y, and y = X — = x. 0.28398, 
j> j 331 

in which x indicates the weight of the tribromophenol found in the 
amount of the urine employed, and y the corresponding quantity of 
phenol. 

Method : 500-1000 c.c. of urine are treated with one-fifth of this 
amount of dilute hydrochloric acid and distilled as long as a specimen 
of the distillate is rendered cloudy by the addition of bromine-water 
(1 : 30), the specimens used for this purpose being carefully pre- 
served. The total quantity of the filtered distillate, together with 
the specimens which have been set aside, is now treated with bromine- 
water, shaking the mixture after each addition of the reagent until a 
permanent yellow color results. Beyond this point a further addition 
of bromine-water is beset with danger, as compounds will be formed 
which contain more bromine, the presence of which would indicate a 
smaller amount of phenol than that actually contained in the urine. 
After two or three days the precipitate is collected on a filter which 
has been dried over sulphuric acid, washed with water containing a 
trace of bromine, and then dried over sulphuric acid and weighed. 
The drying over sulphuric acid is necessary, as tribromophenol is 
fairly volatile, and a vacuum hence inadmissible. 



THE URINE. t<,7 

Pyrocatechin. Urines containing pyrocatechin, like those con- 
taining hydrochinon (see above), darken upon standing, though pre- 
senting a normal color when voided. For the demonstration o! 

these bodies in the urine the reader is referred to special works upon 
urinary analysis. 

Acetone. Acetone may at the present time be regarded as a nor- 
mal urinary constituent, its quantity varying Irom an infinitesimally 
small amount to 0.01 gramme pro die. This quantity is materially 
influenced by the nature of the food ingested, a purely albuminous 
diet, for example, if continued for forty-eight hours or longer, causing 
a decided increase. The carbohydrates in all probability have nothing 
whatsoever to do with the production of acetone, and while diacetie 
acid in some cases may be regarded as the mother-substance of acetone, 
this holds good for only a certain percentage of cases, since acetone is 
not infrequently observed during the absence of diacetie acid from the 
urine, as, for example, in the course of a purely albuminous diet; here, 
in fact, the absence of diacetie acid is constant during health. In what 
manner these two substances, which are almost always associated in 
disease, are related to each other, it is impossible to say at the pres- 
ent time. The conditions under which acetonuria, understanding 
thereby a pathologic excretion of acetone, may be observed, are prac- 
tically given by stating that acetonuria is always due to increased 
albuminous decomposition. 

According to v. Jaksch, the following divisions may be made : 
febrile, diabetic, cachectic, and psychotic acetonuria, as also that of 
inanition. The reason why acetone appears in these conditions is 
quite clear from what has been said. 

Most important is the diabetic form of acetonuria, and for some 
time it was even held that diabetic coma was due to an accumulation 
of acetone in the blood. However this may be, there appears to be 
no doubt that the association of sugar and acetone in the urine always 
warrants the diagnosis of diabetes mellitus. The amount of the 
latter substance actually seems to stand in a direct relation to the 
intensity of the disease, the maximum excretion being usually asso- 
ciated with a fatal termination. Diacetie acid in such cases is usu- 
ally present at the same time in large amount. In mild cases, on 
the other hand, diacetie acid is absent and the amount of acetone not 
increased. 

Among the febrile diseases in which acetonuria has been observed 
may be mentioned typhoid fever, pneumonia, scarlatina, measles, 



408 CLINICAL DIAGNOSIS. 

acute miliary tuberculosis, acute articular rheumatism, and septicae- 
mia, while in febrile diseases of short duration, even if the degree of 
the fever be high, as in acute tonsillitis, intermittent fever, the hectic 
fever of chronic phthisis, etc., acetonuria is not observed. 

In certain nervous diseases, as in general paresis, melancholia, fol- 
lowing the seizures of epilepsy, and in tabes, acetonuria is frequently 
observed. Just as in these, so also in cases of Addison's disease, 
general carcinomatosis, eclampsia, etc., the acetonuria is always to 
be referred to increased albuminous destruction. 

Finally, the possibility of the occurrence of an enterogenic form 
of acetonuria must be borne in mind, the production of acetonuria 
by the continuous administration of white of eggs certainly strongly 
favoring such a view. Cases of asthma acetonicum and aceton- 
emia possibly belong to this class. 

Tests for Acetone. Legal 1 8 test. This test may be applied to 
the freshly voided urine, but is not conclusive. Several c.c. of urine 
are treated with a few drops of a strong solution of sodium-nitro- 
prusside and sodium hydrate, when the mixture will present a red 
color, which rapidly disappears, and in the presence of acteone is 
replaced by a purple or violet-red upon the addition of acetic acid. 
As a rule, it is safer to distil the urine (500-1000 c.c.) after the 
addition of a little phosphoric acid (1 gramme pro liter), and to 
employ the first 10-30 c.c. of the distillate for the following tests : 

Lieben's test. A few c.c. of the distillate are treated with several 
drops of a dilute solution of iodo-potassic iodide and sodium hydrate, 
when in the presence even of traces of acetone a precipitation of 
iodoform in crystalline form occurs, which may be readily recog- 
nized by its odor. 

Reynold's test. A few «.c of the distillate are treated with a 
small amount of freshly precipitated yellow oxide of mercury. This 
is prepared by precipitating a solution of bichloride of mercury with 
an alcoholic solution of sodium hydrate. If acetone be present, a 
black color, due to the formation of sulphide of mercury, will result 
in the clear filtrate upon the addition of a few drops of ammonium 
sulphide. 

For the quantitative estimation of acetone the reader is referred to 
special works upon urinary analysis. 

Diacetic Acid. The occurrence of diaeetic acid in the urine 
must always be regarded as abnormal. Its pathologic significance 
is identical with that of acetonuria. It is found especially in diabetes, 



TEE URINE, 

in various forms of digestive disturbance, and in febrile diseases. In 

the high and continued fevers of childhood it is almost constantly 

present. 

In order to demonstrate the presence of diacetic acid a few <•.<•. 
of urine are treated with a strong solution of perchloride of iron, 
added drop by drop. Should a precipitation of phosphates occur, 
these are filtered off, when more of the iron solution is added to the 
filtrate. If now a Bordeaux-red color appears, another portion of 
the urine is boiled and similarly treated. [f in this second test no 
reaction is obtained, a third portion of the urine should he treated 
with sulphuric acid and extracted with ether. A positive reaction, 
when the ethereal extract is tested with perchloride of iron, the 
color disappearing upon standing for twenty-four to forty-eight 
hours, will then indicate the presence of diacetic acid, particularly 
if the urine at the same time be rich in acetone. 

Oxybutyric Acid. The fact that in some cases of diabetes 
an excessive elimination of ammonia was observed led to the belief 
that there must be present an unknown acid; this was finally shown 
to be ,5-oxybutyric acid. The occurrence of this acid in the urine 
of diabetic patients is of great clinical interest, as a probable con- 
nection has been established between its presence in the blood and 
diabetic coma. The latter condition is explained by assuming that 
the diabetic patient is unable to furnish sufficient quantities of am- 
monia to neutralize the acids formed in the tissues of the body, the 
alkalies of the blood being consequently attacked. A prophylactic 
treatment with alkalies, such as intravenous injections, has hence 
been suggested in severe cases, with an encouraging degree of suc- 
cess. This, however, is still a mere theory, and the fact that a 
case of diabetic coma has been reported in which the alkalinity of 
the blood was not diminished, and in which recovery took place 
without the use of alkalies, renders the correctness of the hypothesis 
rather doubtful. Possibly the cause of the coma is due to the pres- 
ence of toxins circulating in the blood, causing an increased tissue- 
destruction, with a simultaneous formation of abnormal acids. 

The presence of oxybutyric acid may always be regarded as indi- 
cating a severe type of the disease, and when associated with marked 
acetonuria and diaceturia as indicating danger of coma. 

The presence of oxybutyric acid may be inferred in diabetic urines, 
if after fermentation a rotation of the plane of polarized light to the 
left is observed. 



410 CLINICAL DIAGNOSIS. 

Lactic Acid. Sarco-lactic acid is normally absent from the urine, 
but is met with in pathologic conditions, and particularly in cases of 
hepatic disease, the liver normally being concerned in the decomposi- 
tion of lactic acid, and lactates that may have been introduced into 
the body together with the food. 

In order to test for lactic acid the urine is evaporated on a water- 
bath to a thick syrup and extracted with 95 per cent, alcohol. 
This is decanted off after twenty-four hours, evaporated to a syrup, 
acidified with dilute sulphuric acid, and extracted with ether as long 
as this presents an acid reaction. The ether is then distilled off, and 
the residue dissolved in water. This solution is treated with a few 
drops of basic acetate of lead, filtered, the excess of lead removed by 
means of sulphuretted hydrogen, and the filtrate evaporated to dry- 
ness on the water-bath, when the lactic acid will remain behind as a 
slightly yellowish syrup. This is then dissolved in a little water, 
the solution saturated with zinc carbonate, and heat applied. Zinc 
lactate will separate out upon evaporation and may be recognized by 
the form of its crystals, viz. , small prisms. 

Volatile Patty Acids. The term lipaciduria has been applied by 
v/Jaksch to an increased elimination of volatile fatty acids in the urine 
which is observed at times in cases of fever, hepatic diseases affecting the 
proper structure of the liver, and in diabetes. Clinically, lipaciduria is 
of no especial significance. Traces of fatty acids are also found under 
normal conditions, and are probably formed in the lower segment of 
the small intestine. The fatty acids which have thus far been isolated 
from the urine are formic, acetic, butyric, and propionic acids. They 
may be demonstrated in the same manner as described in the chapter 
on Feces. 

Chyluria. The term chyluria has been applied to a condition in 
which a turbid urine presenting the macroscopic appearance of milk 
is excreted. Upon microscopic examination it may be demonstrated 
that the turbidity in such cases is owing to the presence of innumer- 
able highly refractive globules of fat, which may be removed from the 
urine by shaking with ether. Of other morphologic constituents 
leucocytes are occasionally encountered in large numbers. Red 
blood-corpuscles are also seen at times, and when present in large 
numbers impart a rose color to the urine. Fibrinous coagula are often 
observed when the urine has stood for some time, and the entire 
bulk of urine may even become transformed into a gelatinous mass. 
Albumin is present in most cases in the absence of other constituents 



THE URINE, 41 | 

pointing to renal disease, such as tube-casts and renal epithelial cells. 
Leucin, tyrosin, and cholesterin may at times also be present, par- 
ticularly the latter. It was formerly quite generally accepted thai 
this condition was due to the presence of the filaria sanguinis 
hominis, but while tilarise are undoubtedly present in the blood in 
the majority of instances, and may also be present in the urine, it 
has been demonstrated that cases occur in which filariasis does not 
exist, and Gotze expressed the opinion that chyluria may be owing 
to distinct anatomical lesions affecting the renal parenchyma. Fur- 
ther observations, however, are necessary in order, not only to dear 
up the etiology of the disease, but also the manner in which fat and 
albumin enter the urine. 

Ferments. Ferments may be demonstrated in every mine both 
under physiologic and pathologic conditions, but are of little clinical 
importance, excepting, perhaps, pepsin, which is said to be absent 
in cases of typhoid fever, carcinoma of the stomach, and possibly 
also in nephritis. In order to demonstrate its presence a small 
flake of fibrin is placed in the urine, and after several hours removed 
to a 2 to 3 p.m. solution of hydrochloric acid. The pepsin, if pres- 
ent, will have become deposited upon the fibrin, and cause the diges- 
tion of the latter in the hydrochloric-acid solution. Diastase, a milk- 
curdling ferment, and one causing the decomposition of urea into 
carbon dioxide and ammonia have also been observed. 

Gases. Every urine contains a small amount of gases, notably 
carbon dioxide, oxygen, and nitrogen, which may be withdrawn by 
means of an air-pump. In pathologic conditions sulphuretted hydro- 
gen is at times also found, constituting the condition spoken of as 
hydrothionuria. It is curious to note in this connection that indigo- 
suria has at times been observed to accompany the hydrothionuria. 
That the latter condition is the result of bacterial activity was shown 
by Miiller, and the simultaneous occurrence of indigo and sul- 
phuretted hydrogen would make it appear that the former arises 
under the same or similar conditions as the latter. The occurrence 
of sulphuretted hydrogen, moreover, is of interest, in so far as a 
retention of the same within the body may exert a toxic action. It 
is not probable that the presence of sulphuretted hydrogen is refer- 
able to an abnormal communication between the gut and the urinary 
passages, and it would appear more likely to be derived from the 
intestinal tract by a process of endosmosis. 

In order to test for sulphuretted hydrogen a strip of filter-paper 



412 CLINICAL DIAGNOSIS. 

moistened with a solution of subacetate of lead and sodium hydrate is 
suspended to a cork, and the tube or vessel containing the urine 
closed with this, when in the presence of the gas the paper will be 
colored a gray or black. 

Ptoami'nes. Toxic substances of a basic nature are found only 
in traces in normal urines. In pathologic conditions, however, and 
especially in the acute febrile diseases, such as typhoid fever, pneu- 
monia, pleurisy, and acute yellow atrophy, large amounts may be 
found, and appear to be identical with those obtained from putrefy- 
ing albuminous material. Bouchard pointed out that these sub- 
stances are in all probability formed in the lower portion of the 
intestinal tract. Diamines, viz., putrescin and cadaverin, have 
been found in the urine in cases of cholera asiatica, pernicious 
anaamia, and in connection with cystinuria. Ptomaines in notable 
amounts have also been demonstrated in the urine of maniacs, and 
the question of autointoxication with substances of this character 
as an etiologic factor in mental diseases is prominently engaging the 
attention of alienists at the present time. The whole subject is one 
of the utmost importance, but, as yet, it must be confessed, wrapped 
in the deepest obscurity. 

In order to demonstrate the presence of ptomaines in the urine, 
the methods suggested by Brieger, Stass-Otto, and Gautier may be 
employed, of which the author can recommend that of Gautier 
particularly. 

Sediments. 

In the chapter treating of the general physical characteristics of 
the urine it was stated that on stauding every urine gradually be- 
comes cloudy, owing to the development of the so-called nubecula, 
which was shown to consist of a few mucous corpuscles, some 
pavement-epithelial cells derived from the urinary and genital pas- 
sages, and under certain conditions of a few crystals of uric acid, 
oxalate of calcium, or both. It was further pointed out that owing 
to a diminution in the acidity of the urine on standiug, in conse- 
quence of an inter-action between the neutral urate of sodium and 
the acid phosphate of sodium, a sediment is thrown down which con- 
sists of acid urate of sodium, and at times of free uric acid (see 
Reaction). Should the reaction of the urine upon being voided be 
alkaline, however, a condition which may occur physiologically, 
when it is dependent upon the ingestion of large quantities of vege- 



THE URINE. 



413 



tables rich in organic salts of the alkalies, but which may also be due 
to amrnoniacal fermentation, those constituents of the urine which 
arc held in solution merely in consequence of the presence of acid 

sodium phosphate are thrown down. In the latter case the sedi- 
ment consists essentially of calcium, magnesium, and ammonium 
salts. Crystals of amnionio-magnesium phosphate, it is true, may 

also be observed in alkaline urines of the first variety, but are then 
almost always due to an increased elimination of ammonia, and hence 
rarely observed in physiologic conditions. 

Normally calcium is found only in combination with phosphoric 
acid and carbonic acid. Of the three possible calcium salts of phos- 
phoric acid—/, e., Ca 3 (PO,) 2 , CaHPO,, and Ca(H 2 P0 4 ) 2 — only the 
former two are found in an alkaline urine, while they may be ob- 
served also in specimens which are either neutral or at least but 
faintly acid. The acid calcium phosphate, Ca(H 2 P0 4 ) 2 , is seen but 
rarely in sediments, and its occurrence always presupposes the exisl 
ence of a high degree of acidity, being precipitated together with 
uric acid, and under similar conditions. Calcium carbonate, CaC0 3 , 
is seen only in neutral or alkaline urines. As soon as ammoniacal 
fermentation has begun, ammonium salts are, of course, formed, viz., 
ammonium urate and ammouio-magnesium phosphate. 

The following table shows the various mineral constituents which 
are usually observed in sediments, the reaction of the urine being in 
every case the all-important factor : 
Reaction acid. 

Uric acid. 

Urate of sodium. 

Oxalate of calcium. 

Primary calcium phosphate. 

Ammonio- magnesium phosphate. 
Reaction alkaline (referable to fixed alkalies). 

Secondary calcium phosphate. 

Tricalcium phosphate. 

Calcium carbonate. 

Ammonio-magnesium phosphate. 
Reaction alkaline (referable to ammonia). 

Ammonium urate. 

Ammonio-magnesium phosphate. 

Tricalcium phosphate. 

Calcium carbonate. 



414 CLINICAL DIAGNOSIS. 

In pathologic conditions still other unorganized substances may 
be observed in urinary sediments, viz., cystin, xanthin, tyrosin, hip- 
puric acid, indigo, urorubin, bilirubin, ha^matoidin, magnesium phos- 
phate, calcium sulphate, cholesterin, leucin, tyrosin, fats, ammonium 
and magnesium sulphate. Of these cystin, xanthin, hippuric acid, 
tyrosin, calcium sulphate, biliruoin, hsernatoidin, magnesium phos- 
phate, leucin, and the soaps of magnesium and calcium occur only in 
acid urines, while indigo, urorubin, and cholesterin are usually found 
only in alkaline specimens. Before considering these various possi- 
ble constituents in detail, it may not be out of place to say a few 
words about sediments in general, and the method to be followed in 
their microscopic examination. 

An idea of the nature of a deposit may often be formed by inspec- 
tion, especially if the reaction of the urine be known. 

A crystalline sediment, presenting a brick-red color, and appear- 
ing to the naked eye like cayenne pepper, observed at the bottom of 
the vessel, is usually referable to uric acid. On the other hand, a 
deep red amorphous deposit occurring in an acid urine will con- 
sist essentially of urates, the color in this case, as in the former, 
being due to uroerythrin. Further proof is hardly required. Should 
any doubt be felt, however, it will only be necessary to heat the 
urine, when the deposit will be seen to dissolve. A white floc- 
culent sediment in an alkaline urine is usually referable to a mix- 
ture of phosphates, carbonates, and alkaline urates, and will dissolve 
without difficulty upon the addition of acetic acid, while it remains 
unaffected by heat. 

A sediment, consisting of pus, occurring in alkaline urines is fre- 
quently mistaken for a phosphatic deposit by the beginner. Aside 
from a microscopic examination this question may be settled by the 
addition of a small piece of caustic soda, and stirring, when in the 
presence of pus the liquid becomes mucilaginous and ropy. If much 
pus be present, a tough, jelly-like mass will be formed, which escapes 
from the vessel as a whole when the urine is poured out. Such a 
sediment, moreover, will not disappear upon the addition of an acid, 
and will be rendered still more dense upon the application of heat. 

Blood, when present beyond traces, may also be recognized. 

Reliance should, however, not be placed upon the macroscopic 
appearance of a sediment, to the exclusion of a careful microscopic 
examination, as those constituents, particularly the morphologic 
elements of a sediment which are of more especial importance, can 



THE URINE, 



II.. 



moreover. 



only be demonstrated in this manner. Aa a general rule, 

it may be said that the unorganized elements of a deposit are usually 

of little clinical interest, as diagnostic conclusions can only rarely be 
drawn from their presence. 

Students are frequently in the habit oi diagnosing an excessive nor- 
mal or subnormal elimination of one or another urinary constituent 
from the result of a microscopic examination. This is unwarrantable, 
and it should always be remembered that no conclusion- whatsoever 
can be drawn in this manner as to the amount actually eliminated, 
for nothing would be more erroneous, for example, than to infer an 
excessive excretion, not to speak of a production, of uric acid or 
oxalic acid from the fact that crystals of these substances are seen in 
large numbers under the microscope. Again and again are cases 
observed in which an excessive elimination of uric acid, oxalic acid. 
or phosphates is diagnosed by mere inspection, and in which a can lid 
chemical analysis shows not only no increase, but even a diminution 
of the normal quantity. 

A urine which is turbid when passed may be examined micro- 
scopically at once. As a rule, however, it is necessary to wait until 
a. sediment has formed. The advice is usually given to allow the 
specimen to settle in a conical glass, to decant off the supernatant 
fluid as soon as a sufficient deposit has been obtained, and to ex- 
amine a drop of the latter upon a slide covered with a cover- 
glass. This recommendation is a good one, and is usually fol- 
lowed. Not infrequently, however, it is necessary to wait for 
twenty-four hours or even longer, until a sufficient deposit has 
formed ; but even when the urine is kept covered it will frequently 
be found that ammouiacal fermentation has taken place, rendering 
the microscopic examination decidedly unsatisfactory. The urine 
should hence be kept in a clean and well-stoppered bottle until the 
desired deposit has formed. A small amount is then removed by 
means of a clean pipette carried down to the sediment with the distal 
end tightly closed with the finger, care being taken not to allow the 
urine to rush into the tube by suddenly releasing the finger, but 
withdrawing only a small amount just sufficient for an examination. 
This is then spread over a clean slide that has been moistened upon 
its surface by the breath, when the specimen may be examined at 
once. Covering the specimen with a slip is not only unnecessary, but 
even undesirable, crushing being thus avoided, while at the sain* tim 
a much larger field is offered to observation at one time. - 1 low pom r 



416 CLINICAL DIAGNOSIS. 

of the microscope should always be employed, and the high power 
reserved entirely for more detailed examination. 



MICROSCOPIC EXAMINATION OF THE URINE. 

Within late years the centrifugal machine has been applied to 
urinary examinations, and whenever it is desirable to obtain a de- 
posit at once, or whenever a deposit separates out so slowly as to 
endanger the integrity of the urine, an apparatus of this kind will be 
found very convenient. Daland's hcematohrit is furnished with an 
attachment for this purpose. 

Non-organized sediments. Sediments occurring in acid 
urines. Uric acid. The form which uric-acid crystals may 
present in a deposit varies greatly, the most common being the 
so-called whetstone-form shown in Fig. 87. The crystals may 
occur singly or arranged in groups. Accidental impurities, such 
as threads or hairs, are at times covered with such crystals, form- 

FlG. 97. 




Colorless crystals of uric acid. 

ing long cylinders. When presenting this form their presence can 
generally not be determined macroscopically. Very frequently, 
however, uric acid crystallizes out in the form of large rosettes 
composed of tube-shaped or long-pointed crystals, presenting a 
deep-red color, referable to uroerythrin, when they are often vis- 
ible to the naked eye, forming the well-known brick-dust sedi- 
ment at the bottom of the vessel. While it is generally stated that 
uric-acid crystals may always be recognized by their color, varying 
from a light yellow to a dark brown, the author has repeatedly 
observed uric acid in sediments, in which the crystals, which in such 



THE URINE 117 

cases formed small rhombic plates with rounded edges, occurring 

singly or several joined together, were absolutely devoid of coloring- 
matter, as far as a microscopic examination went (Fig. 97), [Jrio- 

acid " dumb-bells " are also at times observed, and may be mistaken 
for calcium oxalate. 

Auric-acid sediment is observed in eases in which an increased 
excretion of uric acid occurs, but it should be remembered that, 
as a rule, it is not permissible to infer an increased production 
or elimination from the presence of an abundant deposit of this 
substance alone. Brick-dust sediments are frequently observed in 
the urine during the winter months ; but nothing would be more 
erroneous than to infer an increased elimination from such an ob- 
servation, as the phenomenon in nine cases out of ten is explained 
by the fact that uric acid is far less soluble in cold than in warm 
water. During the summer mouths, for the same reason, a deposit 
of uric acid is far less frequently observed, although an increased 
amount may nevertheless be present, being held in solution owing to 
the higher temperature. The more concentrated the urine and the 
more uric acid it actually contains, however, the more readily will a 
deposit of the kind occur. Whenever more water is eliminated 
through other channels than is consumed or at least absorbed from 
the intestinal mucosa such deposits will occur, and are hence noted 
after profuse perspiration, following severe muscular exercise, in acute 
rheumatism with copious diaphoresis, acute gastritis and enteritis, 
profuse diarrhoea, during the crisis of pneumonia, particularly if ac- 
companied by much sweating, etc. In all these conditions, however, 
an increased elimination of uric acid does not necessarily take place, 
the all-important factors being the reaction of the urine, its degree of 
concentration, and the surrounding temperature. On the other hand, 
it is very common to observe uric-acid sediments in cases in which 
uric acid is actually eliminated in increased amounts. From what 
has been said, however, it is clear that the occurrence of such deposits 
is usually not of much diagnostic interest. 

Should formed concretions of uric acid — i.e., uric-acid grave] — 
be found in the urine, a direct indication is afforded to diminish the 
acidity of the urine, and to increase the amount of water so as to 
guard against the formation of a renal or vesical calculus with it- 
consequences. 

Chemically the nature of a uric-acid sediment may he recognized 
by the fact that the crystals dissolve upon the addition of sodium 



418 CLINICAL DIAGNOSIS. 

hydrate, reappearing again in the rhombic form upon neutralization 
with hydrochloric acid. When heated with dilute nitric acid the 
beautiful red color of ammonium purpurate is obtained upon the 
subsequent addition of ammonia (murexid test), as described else- 
where (see p. 317). 

Amorphous urates. Sodium aud potassium urates frequently, 
especially in fevers, form sediments of such a density that upon 
microscopic examination it is almost impossible to discern anything 
but innumerable amorphous granules scattered over the entire micro- 
scopic field in a most irregular manner, and obscuring all other ele- 
ments that may at the same time be present. Cells or casts that 
might possibly be discovered will frequently be seen to be studded 
with these granules. In such cases it is best to heat the urine to a 
temperature of 50° C, and to filter it as rapidly as possible while 
still hot, the contents of the filter being subsequently used for micro- 
scopic purposes. 

Urate sediments are always colored, the tint varying from a dirty 
brown to a bright brick-red, owing to the presence of uroerythrin. 
Difficulties can hence never arise in determining the nature of the 
sediment, as a colored deposit appearing in an acid urine, which 
dissolves upon the application of heat, cannot be due to anything 
but urates. If a drop of the sediment, moreover, is treated upon a 
slide with a drop of hydrochloric acid, some characteristic whetstone- 
crystals of uric acid will be seen to separate out, while the greater 
portion will appear in the form of rhombic tablets. 

Calcium oxalate. This substance generally appears in urinary 
sediments in the form of small, colorless, highly refractive octahedra 
(Fig. 91), which vary greatly in size, some appearing as mere 
specks even under a comparatively high magnifying power, while 
others may attain the dimensions of a large leucocyte. Frequently 
one axis is longer than the other. From the fact that their diagonal 
planes are very highly refractive, apparently dividing the superficial 
plane into four triangles, they have been compared to envelopes, 
and it is this envelope-form of the crystals which is especially char- 
acteristic. In the same specimen of urine so-called dumb-bell forms 
may be found, which appear to be made up of two bundles of needle- 
like crystals united in the form of the figure 8. The latter, accord- 
ing to Beale, originate in the uriniferous tubules, and are frequently 
found adherent to or imbedded in tube-casts. Other forms may 
also be found, and are shown in the accompanying figure (Fig. 



THE URINE. H«, 

98). In this connection the author wishes to draw attention to the 
occurrence oi curious, highly refractive, more or less angular bodies 
in urinary sediments, which do not promt a well-defined crystal- 
line form, and which he is inclined to regard as an amorphous 
form of calcium oxalate. 

While the envelope crystals arc highly characteristic and can 
hardly be mistaken for any other substance, the student may at 







Fig. 98. 




a 







1 Q 






\> 


%*> ® 


& ®D 


% 


$ 


© ^ 


/ 


Less common forms of oxalate of lime crystals. (Fixlayson.) 



times confound them with crystals of ammonio-magnesium phos- 
phate. Such an error may be avoided if it be remembered that 
the calcium oxalate crystals are never as large as the magnesium 
salt, and that the latter dissolves upon the addition of acetic acid, 
in which calcium oxalate is insoluble. The distinction from uric 
acid, if we are dealiug with the dumb-bell form, cannot always be 
made by mere inspection. A drop of caustic soda should be added, 
which will dissolve the crystals if these be uric acid, while calcium 
oxalate remains unchanged. It has been pointed out that under 
strictly normal conditions a few isolated crystals of calcium oxalate 
may be found in the primitive nubecula, so that their presence in 
urinary sediments cannot be rgarded as pathologic. After the in_ 
tion of certain vegetables and fruits, notably rhubarb, garlic, aspar- 
agus, oranges, or following the continued administration of sodium 
bicarbonate or the salts of vegetable acids, calcium oxalate crystals 
may be observed in large numbers ; so also in certain diseases, such 
as diabetes mellitus, catarrhal jaundice, phthisis, emphysema, etc. 

As in the case of uric acid, no inference can be drawn From a 
microscopic examination of the sediment as to the quantity actually 
eliminated. The frequent occurrence of abundant sediment- of this 
substance may, however, generally be regarded as abnormal, pro- 



420 



CL1XICAL DIAGXOSIS. 



viding that such an occurrence cannot be explained by the nature of 
the diet. It is very suggestive to note the frequency with which such 
sediments are observed in certain cases 01 neurasthenia, associated 
with a mild degree of albuminuria, as also in various digestive neu- 
roses. Finally, as in the case of uric acid, the possibility of the 
formation of renal calculi should be borne in mind, whenever abun- 
dant sediments of calcium oxalate are encountered upon frequent 
examinations, 

Fig. 99. 




■ 
Various forms of triple phosphates. (Fisxaysox.) 




Crystalline phosphates. (Fixlaysox.) 



Ammonio-magnesium phosphate, usually spoken oi as triple phos- 
phate, crystallizes in large prismatic crystals of the rhombic system, 
which are most abundantly observed in alkaline urines, but are also 
quite frequently seen in feebly acid specimens. Of the various 
forms seen (Fig. 100), that resembling the lid of a coffin of the old- 
fashioued type is the most characteristic. (Fig. 99.) The size 



THE URINE. 



42] 



which these crystals at times attain isquite considerable ; very small 
specimens, however, also occur which could possibly be mistaken 
for oxalate of calcium, but from which tbey arc readily distinguished 
by the ease with which tbey dissolve in acetic acid, as has already 
been pointed out. 

Here as elsewhere it should be remembered that no conclusions as 
to the amount actually eliminated can be drawn from a microscopic 
examination, and the diagnosis " Phosphaturia " should only be 
based upon the results of a quantitative analysis. 

Jfonocalcium phosphate crystals are rarely seen and only in spec- 
imens presenting a highly acid reaction, when uric-acid crystals are 
also frequently observed in large numbers. The author observed but 
two cases of this kind, occurring in patients the subjects of functional 



Fig. 101. 




Monocalcium phosphate crystals. 



albuminuria. The urine was highly acid, of a sp. gr. 1.036, and on 
standing deposited a sediment which consisted largely of mono- 
calcium phosphate crystals (Fig. 101) with a considerable number ol 
uric-acid crystals, from which they are readily distinguished by the 
absence of pigment and their solubility in acetic acid. 

Neutral calcium phosphate. These crystals may be found in alka- 
line, neutral, and feebly acid urines. They are at times of large 
size, but more commonly aeicular, occurring either singly or united 
together in a star-like manner (Fig. 99). They are colorless, readily 
soluble iu acetic acid, and insoluble in warm water, so that fchey can 
be easily distinguished from uric acid. 

Basic magnesium phosphate crystals, occurring in the form ol 
large, highly refractive plates (Fig. 102), are at times seen in alka- 
line, neutral, or faintly acid and highly concentrated urines. They 



422 



CLINICAL DIAGNOSIS. 



are readily recognized by treating a drop of the sediment upon the 
slide with a drop of an ammonium carbonate solution (1 : 4), when 
the crystals become opaque and their edges assume an eroded aspect. 
In acetic acid they dissolve with ease and may then be reprecipitated 
by means of sodium carbonate. 



Fig. 102. 




Basic phosphate of magnesia crystals, (v. Jaksch.) 



Hijjpuric-acid crystals have been observed, although rarely, in 
urinary sediments in acute febrile diseases, diabetes, and chorea, 
while their occurrence following the ingestion of large amounts of 
prunes, mulberries, blueberries, or the administration of benzoic acid 
and salicylic acid is more common. 

Hippuric acid occurs in the form of fine needles or rhombic prisms 
and columns, the ends of which terminate in two or four planes, at 



times resembling the crystals of 



phosphate 



Fig. 103. 




Calcium sulphate crystals, (v. Jaksch.) 



and of uric acid. From the former they may be readily dis- 
tinguished by their insolubility in hydrochloric acid, and from the 
latter by the fact that they do not give the murexid reaction when 
treated with nitric acid and ammonia (see p. 317). In the case of 
urines rich in hippuric acid, in which this does not appear in the 



THE URINE. l-.i 

sediment, it is well to add a small amount of hydrochloric acid, 
when the crystals will gradually separate out, A> pel their pres- 
ence docs not appear to possess any clinical significance. 
, Calcium sulphate in the form of long colorless needles or elongated 

prismatic tablets (Fig. 103) lias been observed in urinary sedi- 
ments in only two cases. It may be recognized by its insolubility 

in acids and ammonia. In both cases the mine, especially on stand- 
ing, deposited a milky-looking sediment, the reaction being Btrongly 
acid. 

Oystin, the chemical formula of which is (< ',1 1,NSi u,, must be 
regarded as an amido-acid, and, according to the observation- of 
Baumann, as a normal constituent of the urine. The quantity 
eliminated in the twenty-four hours, however, is very small, amount- 
ing to not more than 0.01 gramme pro liter. In urinary sediments 
cystin is never found under normal conditions, while pathologically 
its occurrence appears to be intimately associated with the simul- 
taneous formation of certain diamines. These, viz., putrescin, cadav- 
erin, and a third diamine, which is isomeric with the latter, are 
formed in the intestinal tract, and are eliminated in the urine as 
well as in the feces. There can be little doubt that the causes 
which give rise to the formation of the one are also responsible for 
the presence of the other, and that the occurrence of cystinnria is 
thus dependent to a large degree at least upon a certain specific form 
of intestinal putrefaction. Beyond this, however, practically noth- 
ing is known of the relation existing between these bodies. 

Clinical interest in connection with cystinuria centres in the fre- 
quent association of cystin sediments with cystin gravel or calculi, 
but it is curious to note that the cystinuria, even after removal of 
the calculus, may persist for years without giving rise to symptoms 
denoting the existence of a pathologic process. Cystin concretion- 
and calculi must be regarded as medical curiosities, as not more 
than about fifty cases of this kind have so far been described. 

Urine containing cystin in pathologic amounts may be of normal 
appearance, reaction, odor, and specific gravity, but is often de- 
scribed as presenting a yellowish-green color, a higher specific 
gravity than normal, and a curious odor. When undergoing putre- 
faction a marked odor of sulphuretted hydrogen develop- o\\ in 
the decomposition of the cystin. When treated with acetic acid, a 
white crystalline sediment separates upon standing, which is soluble 
in ammonia, and from which the crystals usually observed in the 



424 



CLINICAL DIAGNOSIS. 



sediment of the native urine may be obtained upon evaporating the 
ammonia. 

The appearance of these crystals (Fig. 104), which take the form 
of small, colorless, hexagonal plates, and are frequently superimposed 
upon one another, is quite characteristic. If any doubt exist, it 
should be remembered that uric acid, with certain forms of which 
cystin might possibly be confounded at first sight, gives the murexid 
reaction and is insoluble in hydrochloric and oxalic acids, in which 
cystin dissolves with ease, as also in ammonia, from which the 
crystals separate out again upon evaporation, as just described. 

Fig. 104. 




Crystals of cystin spontaneously voided with urine. (Roberts.) 



Cystin crystals, when tested upon platinum foil, burn with a 
bluish-green flame without melting. 

To determine the amount of cystin, the urine should be treated 
with an excess of acetic acid, as directed, and the sediment which 
forms upon standing, filtered off, washed with water, dried over 
sulphuric acid, and weighed. This method is not very exact, as not 
all the cystin is obtained, but it is the only one available. Should 
uric acid be present in the sediment, the cystin must be separated 
i'roni this by dissolving it in ammonia. Mucin may be removed by 
previously adding neutral acetate oi' lead. 

Leucin and tyrosin, which both belong to the group of amido- 
acids, being represented by the formulae C 6 H 13 N0 2 and C 9 H n K"0 3 , 
respectively, are never found in the urine under normal conditions. 



THE UBINE. 



125 



Their presence, indeed, may be regarded as pathognomonic of 
acute yellow atrophy of the liver, excepting, perhaps, some rare 
cases of acute phosphorus-poisoning associated with hepatic atrophy, 
notwithstanding statements to the contrary, according to which these 

substances may also be encountered in cases of amir hepatic atrophy 
referable to other causes, in typhoid fever, variola, etc. In two 
cases of so-called malignant jaundice, in which a most rapidly pro- 
gressing atrophy of the liver was noted, the author was unable to 

detect either of these bodies, notwithstanding a most careful chemi- 
cal examination. In acute phosphorus-poisoning, moreover, Leucin 
and tyrosin are not as a general rule found, so that in the differential 
diaguosis between this condition and acute yellow atrophy the pres- 
ence of these bodies may be regarded as indicating the existence of 
the latter disease. The fact that urea may be altogether absent from 
the urine in cases of acute yellow atrophy, or present in greatly 
diminished amount, has already been referred to (see Urea, p. 293), 
and the elimination of leucin and tyrosin, in its stead, as it were, has 
been regarded not only as indicating the probable origin of urea 
from amido-acids, but also the formation of urea, to a large extent, 
at least, in the liver. The albuminous origin of these substances has 
likewise been noted (see Urea). 

Fig. 105. 




/ V 

Tyrosin crystals. (Charles.) 

As leucin is hardly ever found in the sediment, and tyrosin only 
when present in large quantities, the urine in every case should firsl 
be concentrated upon a water-bath, and examined on cooling. At 
times, however, when these substances are present in only very small 
quantities, this procedure may not lead to the desired end. and in 
doubtful cases the following method should be employed. 

The total amount of urine voided in twenty-lour hours is pre- 
cipitated with basic acetate of lead and filtered, when the filtrate. 



426 



CLINICAL DIAGNOSIS. 



from, which the excess of lead has been removed by means of sul- 
phuretted hydrogen, is evaporated to as small a volume as possible 
and set aside for crystallization. The residue thus obtained is then 
microscopically examined, and if crystals be detected which answer 
the description of tyrosin and leucin, they should be subjected to 
further chemical tests. 

Tyrosin crystallizes in the form of very fine needles (Fig. 105), 
which are usually grouped together in sheaves or bundles, crossing 
each other at various angles. They are insoluble in acetic acid, but 
soluble in ammonia and hydrochloric acid. 

Leucin (Fig. 106) occurs in the form of spherules of variable size, 
which closely resemble globules of fat, but may be distinguished 
from these by their insolubility in ether.. They present a more or 
less pronounced brownish color, and upon close examination con- 
centric striations as well as very fine radiating lines can at times be 
made out, the latter being especially characteristic. 



Fig. 106. 




Crystals of leucin (different forms) . (Crystals of creatinin chloride of zinc resemble the 
leucin crystals depicted at a.) The crystals figured toward the right consist of comparatively 
impure leucin. (Charles.) 



If crystals resembling tyrosin and leucin be found, the following 
procedure should be employed : 

In order to separate the leucin from the tyrosin, the residue is 
treated with a small amount of alcohol, in which leucin is more 
readily soluble than tyrosin. 

Tests for tyrosin. The sediment is filtered off, washed with water, 
and dissolved in ammonia, to which a little ammonium carbonate 
has been added. This solution is allowed to evaporate, leaving the 
tyrosin behind. 

Piria's test. A bit of the tyrosin is moistened on a watch-crystal, 
with a few drops of concentrated sulphuric acid, covered, and set 



THE URINE. l-j; 

aside for half an hour. It is then diluted with water, heated, and 
while hot, saturated with calcium carbonate and filtered. The ni- 
trate is colorless, and when heated with a lew drops of a very dilute 
solution of perchloride of iron, which must be Tree from hydrochloric 
acid, it assumes a violet tint (v. Jaksch). 

Hoffmann's test. A small amount of tyrosin, when dissolved in 
hot water and treated, while hot, with mercuric nitrate and potassium 
nitrite, imparts to the solution a beautiful dark-red color, and causes 
the appearance of a voluminous red precipitate. 

Tests for leucin, Scherer's test. To test for leucin, this is sepa- 
rated from tyrosin, as described, by the addition of a little alcohol. 
The alcohol is allowed to evaporate, and a portion of the residue 
treated upon platinum-foil with nitric acid, when a colorless residue 
is obtained, which, upon the application of heat and a few drops of a 
solution of sodium hydrate, forms a droplet of an oily fluid which 
does not adhere to the platinum. 

Hofmeister's test. A small amount of leucin dissolved in water 
causes a deposit of metallic mercury when heated with mercurous 
nitrate. 

Fig. 107. 







o 



a. Crystals of xanthiu (Salkowski) ; b. Crystals of cystin (Rodin i. 

Xaathin crystals (Fig. 107) are very rarely observed in urinary 
sediments, and, as far as could be ascertained, the case observed by 
Bence Jones is the only one on record. Care should be had not to 
confound certain forms of uric acid with xanthin,and the author well 
remembers an instance in which crystals were observed identical in 
appearance with those here pictured, which upon chemical examina- 
tion, however, proved to be uric acid. The necessity of disregarding 
the statement generally made that uric-acid crystals found in urinary 
sediments are invariably colored cannot h<- insisted upon too strongly. 
It has been elsewhere indicated that uric-acid crystals which are color- 
less may be encountered, and in the case just cited this was observed. 



428 



CLINICAL DIAGNOSIS. 



Cliuically, xaDthia sediments are of interest only in so far as this 
substance may give rise to the formation of calculi, and in the case 
observed by Bence Jones attacks of renal colic had occurred several 
years previously. 

Soaps of lime and magnesia, v. Jaksch has pointed out that in 
various diseases crystals may be found which " closely " resemble 
ty rosin in appearance, and pictures such crystals (Fig. 108), which 
from their behavior toward reagents he is inclined to regard as cal- 
cium and magnesium salts of certain higher fattv acids. 



Fig. 108. 




Lime and magnesium soaps, (v. Jaksch. 



Should any doubt arise, the question may be readily decided by a 
chemical examination (see tests for ty rosin and fatty acids). 

Bilirubin crystals in the form of yellow or ruby-red rhombic plates 
or needles, as well as amorphous granules, have been seen in the 
urine in rare cases, but are of no special interest. They are easily 
soluble in alkalies and chloroform, but not in ether. AVhen treated 
upon a slide with a drop of nitric acid, a green ring will be seen to 
form around them. (Gmelin's reaction.) 

Hcematoidin crystals, which cannot be distinguished from bilirubin 
by the microscope, and also resemble the latter chemically to such a 
degree that Hoppe-Seyler regarded them as indistinguishable from 
each other, are almost as rarely seen as the former. They may 
be seen either free or imbedded within cells or tube-casts in cases 
of scarlatinal nephritis, the nephritis of pregnancy, in granular 
atrophy and amyloid degeneration of the kidneys, and in carcinoma 



THE UBINR |2g 

of the bladder, of which latter condition they have been regarded by 
some as pathognomonic. 

It has been stated that hsematoidin crystals may be distinguished 

from bilirubin crystals by the occurrence oi a transient blue color 
when treated with nitric acid, but v. Jaksch rightly regards tins re- 
action as of doubtful value, as a blue color is similarly obtained 
when bile-stained elements of a urinary sediment are treated in tins 
manner. 

Fat Whenever small strongly refractive globules of Tat, which 
may be readily recognized by their solubility in ether, arc observed, 
either floating on top of the urine or held in suspension, it is n 
sary to ascertain first of all whether such fat may not have been 
introduced into the urine accidentally, owing to the use of a bottle or 
vessel not absolutely clean, previous catheterization, etc. The diag- 
nosis " Lipuria" should only be made when all possible precautions 
to insure against the accidental presence of this substance have been 
taken. Every physician who has occasion frequently to examine 
urines has undoubtedly met with instances in which fat-globules 
were found, and in which a careful inquiry showed that these were 
only accidentally present. Lipuria — i. e. y an elimination of fat usually 
in the form of minute droplets floating in the urine — has been noted in 
various cachectic conditions, in cases of heart-disease, affections of the 
pancreas and liver, in gangrene, and pyaemia, associated with diseases 
of the bones, especially following fractures, in diseases of the joints, 
etc. Fat has also been observed in the urine following the inges- 
tion of large amounts of cod-liver oil and inunctions with fats and 
oils. 

In cases of fatty degeneration of the kidneys, in Bright's disease, 
phosphorus-poisoning, etc., minute droplets of fat are seen in the 
epithelial cells and tube-casts, so minute at times that they appear 
as mere granulations; the exact nature of these formations can 
only be determined by a chemical examination — i.e., by treating the 
preparation with ether, in which they readily dissolve. The occur- 
rence of fat-droplets in the morphologic elements of a urinary sedi- 
ment should not, however, be regarded as constituting a form of 
lipuria. 

The largest amounts of fat are observed in chyluria, a condition 
due to the presence of a distinct parasite in the blood, the filaria 
sanguinis hominis, or more rarely the distoma haematobium, which 
has been referred to in the chapter on Blood (see Chyluria). 



430 CLINICAL DIAGNOSIS. 

Sediments Occurring in Alkaline Urines. Basic phos- 
phates of calcium and magnesium. The most common sediments ob- 
served in alkaline urines consist of amorphous phosphates of calcium 
and magnesium. They are usually as abundant as the urate sedi- 
ments mentioned, but may be readily distinguished from these by the 
fact that they do not dissolve upon the application of heat, but readily 
disappear upon the additiou of acetic acid, and are never colored. In 
this manner it is also easy to distinguish such a sediment from one 
due to pus, with which it might possibly be confounded at first sight. 
Upon microscopic examination a drop of the sediment will be seen to 
contain innumerable transparent granules, scattered over the entire 
field, closely resembling those of urate of sodium and potassium. 

Phosphate sediments are observed, as mentioned elsewhere, when- 
ever the reaction of the urine is alkaline, be this owing to the pres- 
ence of fixed alkalies or to ammoniacal fermentation. 

Fig. 109. 



^ 



CP 




Ammonium urate crystals 



Ammonium urate is observed only in urines which are under- 
going ammoniacal fermentation. Its presence should always call for 
a careful investigation in order to ascertain whether this has taken 
place after the urine has been voided or before (see Reaction). 

The salt occurs in the form of colored spherical bodies of variable 
size, which are frequently beset with prismatic spicules, and are not 
easily mistaken for any other substance which may be present in 
urinary sediments (Fig. 109). It is characterized, moreover, by its 
solubility in acetic and hydrochloric acids, and the subsequent sepa- 
ration of rhombic crystals of uric acid. 

Magnesium phosphate has been described above (see p. 421). 



THE URINE. 



431 



Ammonio-magnesium jthosphate While the well-known coffin-lid- 
shaped crystals are commonly seen in feebly acid urines, as pointed 
out, ammonio-magnesium phosphate presents a great variety of forms 
in alkaline urines, especially in specimens undergoing ammoniacal 
fermentation, those resembling flakes of snow being the most common 
(see Fig. 99). 

Calcium carbonate occurs frequently in alkaline urines, appearing 
under the microscope as minute granules, occurring singly or ar- 



FiG. 110. 




• Calcium carbonate crystals. 

ranged in masses ; dumb-bell forms are also seen (Fig. 110). They 
may be recognized by the fact that they readily dissolve in acetic 
acid with the evolution of gas. 

Indigo in the form of fine blue needles (Fig. Ill), arranged in a 
stellate manner or in plates, visible only with the microscope, are 
rarely seen, and a specimen, such as the one which v. Jaksch pictures, 




Indigo crystals from a urine rich in indican, after standing for eight days at ordinary 
temperature, (v. Jaksch.) 

can only be regarded as a rare medical curiosity. In an amorphous 
condition, however, indigo may be met with in almost every old urine, 
occurring in the form of small granules, and frequently staining 
morphologic elements that may be present a distinct blue. Sediments 
which present a bluish-black color were already noted at the time of 
Hippocrates, and have since been described by numerous observers, 



432 



CLINICAL DIAGNOSIS. 



although the true nature of the coloring-matter has only been deter- 
mined within the last fifty years. Clinically the occurrence of indigo 
in the urine is of significance ouly in so far as renal calculi have been 
observed which consisted almost entirely of this substance. But little 
is known of the causes which give rise to the appearance of indigo 
in the urine, but there can be no doubt that its occurrence is referable 
to the action of certain micro-organisms upon urinary indican. 

Organized Constituents of Urinary Sediments. 

Epithelial Cells. (Fig. 112.) Bearing in mind the fact that 
desquamative processes are constantly going on in the epithelial 

Fig. 112. 




Epithelium from the urinary passages. 



lining of the various cavities and channels of the body, one should 
expect to find in every urine representatives of the different forms 
of epithelium occurring in the urinary organs, from the Mal- 
pighian tufts down to the meatus urinarius. To a certain extent 
this actually happens, and cells apparently derived from the meatus, 



THE URINE. 433 

the urethra, bladder, ureters, aud pelvis of the kidneys may be 
met with in almost every specimen, although it may at times be 
difficult to refer the individual cells observed to their proper origin. 
Bizzozero even claims that it is impossible to distinguish between 
the cells of the bladder and those of the meatus and renal pelvis, 
while, as a class, they may readily be differentiated in most cases 
from the cells of the urethra, the ureters, the prepuce of the male 
and the vulva and vagina of the female. Cells from the uriniferous 
tubules of the kidneys, on the other hand, are seldom seen in normal 
urines, and when they do occur it is impossible to determine their 
exact origin; i.e., the particular portion of the tubule from which 
they have been detached. Cells presenting the characteristic striated 
appearance seen in the irregular, and to a less evident degree in the 
convoluted portions of the uriniferous tubules are never observed in 
the urine. This fact, as well as the usual absence of true glandular 
cells from the urine, remains as yet to be explained. It does not 
appear improbable that the absence of these cells may be referable 
to a less marked degree of desquamation going on in those parts, in 
which the mechanical injury to which the epithelium is subject must 
of necessity be far less severe than in the remaining portions of the 
urinary tract, and particularly in the bladder and urethra. 

As has been stated elsewhere, the number of epithelial cells occur- 
ring in urinary sediments under physiologic conditions is small, and 
the presence of large numbers may hence always be regarded as patho- 
logic, indicating the existence of a circulatory or inflammatory dis- 
turbance affecting some portion of the urinary tract. 

Were it possible in every case to determine the exact origin of 
the cells observed, it is clear that information of great value could 
thus be obtained, and that it would be a comparatively simple 
matter to localize the seat of a lesion. Unfortunately this is not 
always possible, as the form of the cells is dependent to a certain de- 
gree upon the reaction of the urine, an alkaline or neutral reaction 
causing the cells to swell, and to appear larger and rounder than is 
the case in acid urines. As has been mentioned, the cellular type is 
practically the same in the bladder, ureters, and pelvis of the kid- 
neys. 

Definite conclusions should hence be drawn only exceptionally 
from a microscopic examination alone, but there can be no doubt 
that in conjunction with other factors and the clinical history the 
demonstration of a normal or increased number of epithelial cells 

28 



434 CLINICAL DIAGNOSIS. 

may frequently be of decided value in a differential diagnosis, and 
taking these factors into consideration it may even be possible to 
localize the seat of the lesion. If attention be directed to the struct- 
ure of the individual cell, and this holds good more especially for 
the cells derived from the uriniferous tubules, an idea may at times 
even be formed of the character of the lesion (see below). 

Ultzmann recognizes three forms of epithelial cells which may be 
found in urinary sediments, viz. : 

1. Round cells. 

2. Conical and caudate cells. 

3. Flat cells. 

Round cells are usually derived from the uriniferous tubules, 
and the deeper layers of the mucous membrane of the pelvis of the 
kidneys. In the urine they present a more or less rounded form 
and are provided with a distinct nucleus, being not much larger than 
pus-corpuscles, from which latter they may be distinguished very 
readily by the presence of a well-defined nucleus, which in pus-cells 
becomes distinct only upon the addition of acetic acid, and, more- 
over, is polymorphous. Whenever such cells are found adhering to 
urinary casts, which latter may at times consist entirely of these 
structures, it is clear that they represent the glandular elements 
proper of the kidneys. -As similar cells are found in the male 
urethra, some confusion may possibly arise. Should albumin, how- 
ever, be present the probabilities are that the cells are of renal origin. 
The presence of such cells in large numbers together with pus, in the 
absence of tube-casts and albumin, beyond traces, wdll usually indicate 
the existence of a simple pyelitis, particularly if rouud cells are found 
joined together in a shingle-like manner. Should the pyelitis be 
associated with a nephritis, tube-casts and albumin in large amounts 
will at the same time be present. In such cases it may be impossi- 
ble to determine the origin of the cells, excepting of such that may 
be adhering to tube-casts. In simple circulatory disturbances affect- 
ing the renal parenchyma no special abnormalities can be discovered 
in the structure of the cells, while in cases of fatty degeneration of the 
kidneys they will be seen to contaiu fatty particles in greater or less 
abundance, so that it may be possible to determine the existence 
of degenerative processes which may be of inflammatory or non- 
inflammatory origin. The same may be said to hold good if the 
epithelial elements are markedly granular and occur in fragments. 

Conical and caudate cells are mostly derived from the superficial 



THE URINE. 435 

layers of the pelvis of the kidneys, and are hence seen especially in 
cases of pyelitis. Similar cells are also found in the neck of the 
bladder, and may usually be distinguished from those of the pelvis 
by the greater length of their processes. 

Flat cells may come from the ureters, the bladder, the prepuce oi 
the male, and the vulva and vagina of the female. These cells pre- 
sent the usual characteristics of squamous epithelium, being large, 
polygonal iu form, and provided with a well-defined nucleus, the 
extra-nuclear protoplasm being only slightly granular. Other more 
or less rounded forms are also seen which are derived from the deeper 
layers of the mucosa, but are readily distinguished from the small 
round-cells of the kidneys proper. Irregular or conical cells, often 
provided with one or more protoplasmic processes, likewise come 
from the lower layer of the mucosa of the bladder and ureters. 

While the cells of the bladder may thus be confounded with those 
of the ureters and vagina under the microscope, it is not likely that a 
vaginitis or vulvitis will be mistaken for a cystitis or a ureteritis. 
In doubtful cases specimens of urine should be procured by means 
of the catheter, care first being taken carefully to cleanse the vulva. 
The warped appearance so frequently seen in vaginal epithelial cells, 
and the fact that these often and indeed usually appear in masses, 
may further aid in the differential diagnosis. 

It has been pointed out by Peyer that the presence of pavement- 
epithelial cells, together with mucus and leucocytes, in the urine of 
hysterical and anaemic girls may be regarded as indicating an irri- 
tated condition of the genitals, possibly in consequence of masturba- 
tion. Bearing in mind the moist and sensitive condition of the 
vulva of female masturbators, such a view appears plausible. 

A ureteritis, notwithstanding the fact that the ureteral cells closely 
resemble those of the bladder, may be inferred indirectly, the pres- 
ence of squamoifs cells in abundance pointing to a cystitis ; a small 
increase in their number to ureteritis. In conclusion it should be 
stated that the so-called mucous corpuscles present in every urine 
are nothing more than the youngest vesical cells. 

From what has been said it is clear that with due precautions and 
taking other factors into consideration, the discovery of epithelial 
cells in large numbers in urinary sediments may be of decided value 
in diagnosis. 

Leucocytes. Leucocytes are only encountered in very small 
numbers in normal urines. A marked increase should, hence, 



CLINICAL DIAGNOSIS. 

always be regarded as indicating the existence of disease somewhere 

in the course of the urinary tract, excepting in females, when their 

-ence may be owing to an admixture of leueorrhceal discharge. 

In the latter case the source of the pus will generally be recognized 

by the simultaneous occurrence of pavement-epithelial cells of the 
vaginal type in correspondingly large numbers. In doubtful cases 
the urine should always be obtained with the catheter, care first being 
taken carefully to cleanse the vulva. 

Occasionally the pus is derived from a neighboring abscess that 
has opened into the urinary passa^s. 

The amount of pus found in urines may vary con- On 

the one hand, - sits several cm. in height are not at all uncommon. 
and closely resemble deposits of pb jsphat :~ in appearance, for which 

f are indeed frequently mistaken : on the other hand, it may only 
be possible to discover its presence by means of the microscope, 
which should be employed in every case. 

The appearance of the pns-c rpuscles likewise varies in diff< 
cases : In acid urines their form is usually well preserved, and in 
feebly alkaline and neutral specimens it may even be possible to ob- 
serve amoeboid movement- when :^r slide is carefully warmed. In 
alkaline urines, however, they usually swell up and become opaque. 
- that it is impossible to discern their nuclei unless they are treated 
with acetic acid. At other times, and particularly when pus has 
long remained in the body, as where a neighboring abscess has burst 
the urinary ] iss ges, it may be almost impossible to make out 
a nucleus, and in extreme instances nothing but a mass of granular 
and fatty detritus is encountered. 

While with a certain degree of experience it is hardly likely 
that a distinct sediment of pus will be mistaken for anything else. 
such as a deposit of phosphates, it should be remembered that if 
pus be exposed to the action of ammonia, or an ammonium salt, the 
pus-corpuscles become disintegrated. In such cases, as in cyst'::-, 
in wbicn ammoniacal decomposition of the urine is taking place 
in the blad leposit may be obtained which macroscopic-ally 

resembles mucus, and in which pus-corpuscles may not even be 
demonstrable with the microscope. The sediment then escapes as a 
gelatinous, slippery r s& hen the urine is poured from one vessel 
into another. Under such conditions recourse must be had t<:> 
tin chemical tests, as a pyuria might otherwise be overlooked. 



THE URINE. 437 

To this end the following procedure, suggested by Vitali, may be 

employed : 

The urine, after having been acidified with acetic acid, is filtered 
and the contents of the filter treated with a few drops of tincture of 
guaiacum which has been kept from the light, when in the presence 
of pus the filter-paper is colored a deep blue. 

A solution of iodo-potassic iodide may be employed in less ex- 
treme instances. A drop of this solution is added to a drop of the 
sediment upon a slide, when the pus-corpuscles, owing to the pres- 
ence of glycogen, are colored a dark mahogany-brown, while epithelial 
cells, with certain forms of which they might possibly be mistaken, 
assume a light color. 

Donne's pus-test is based upon the fact that the transformation of 
pus into a gelatinous, mucus-like mass, observed in cases of cystitis, 
owing to the action of ammonium carbonate, may also be artificially 
produced by the addition of a small piece of caustic soda and stirring, 
when in the presence of pus in small amounts the liquid becomes 
mucilaginous and ropy, while a gelatinous mass is obtained if the 
pus be abundant. 

From a clinical point of view it is most important to establish the 
source of the pus in every case of pyuria. This may at times be 
difficult, but the following data will be found of great value in a 
differential diagnosis : 

1. In diseases affecting the renal parenchyma the amount of pus, 
as a rule, is small, except where a large abscess located in the kidney 
structure proper has suddenly burst into the pelvis of the kidney. 

In uncomplicated cases it is a comparatively easy matter to recog- 
nize the renal origin of the pus, as other constituents, such as renal 
epithelial cells, and especially tube-casts, are usually present at the 
same time, and, as was noted in the case of renal epithelial cells, 
leucocytes are quite frequently found adhering to the tube-casts, and 
at times apparently composing these entirely, when they are spoken 
of as pus- casts (see Casts). In nephritis, according to Bizzozero. the 
number of pus-corpuscles stands in a direct relation to the intensity and 
the acute character of the morbid process, the greatest numbers being 
found in cases of acute nephritis, while in the chronic forms their num- 
ber is usually insignificant. Whenever in the course of a chronic 
nephritis large numbers of pus-corpuscles appear in the urine, they 
may be regarded as indicating either an acute exacerbation of the 
disease or a complicating inflammation of some portion of the 



438 CLINICAL DIAGNOSIS. 

urinary tract. In such cases errors may be guarded against by care- 
fully observing the number and character of the epithelial cells 
present at the same time, when it will often be found that what at 
first sight appears as an acute exacerbation of a chronic process, 
judging from the number of pus-corpuscles, is in reality a secondary 
pyelitis, ureteritis, or cystitis. 

In cases of simple renal hyperaemia pus-corpuscles never occur in 
notable numbers. 

2. In pyelitis the amount of pus eliminated may vary consider- 
ably, and at times even perfectly normal urine may be voided, prob- 
ably owing to the fact that the ureter of the affected side, if the 
disease be unilateral, has become obstructed temporarily, when sud- 
denly large quantities may again appear. The diagnosis of pyelitis 
is often difficult, and should be based not only upon the condition 
of the urine, but upon the clinical symptoms, a rule which, of 
course, holds good in other conditions as well. Very significant is 
the fact that the urine in pyelitis is usually acid, a point to be re- 
membered in the differential diagnosis between this condition and 
cystitis, with which pyelitis is quite frequently confounded. A 
careful examination of the epithelial elements present in the urine 
may also be of value, and should never be neglected. Bacteria in 
large numbers are generally present. 

When pyelitis is associated with nephritis it may at times be 
almost impossible to determine the origin of the pus, but if the rule 
set forth above be remembered, that in chronic nephritis the number 
of leucocytes is always small, it is not likely that a pyelitis will be 
overlooked, particularly if the clinical symptoms be taken into con- 
sideration. 

Matters may become still more complicated when a cystitis is 
accompanied by a pyelitis or a pyelonephritis. Catheterization of 
the ureters, the feasibility of which, even in the male, has been 
clearly demonstrated by the late Dr. James Brown, should be re- 
sorted to, and it is highly desirable that this most valuable method 
of diagnosis should become common property as soon as possible. 
Fischl regards the preseuce of cylindrical masses composed of pus- 
corpuscles, formed in all probability in the papillary ducts, as highly 
characteristic of pyelitis. In the examination of a number of cases 
of this kind the author, however, has never been able to demon- 
strate their presence. 

3. A pyuria referable to ureteritis can hardly be diagnosed from 



IKE URINE. 439 

the appearance of the urine, and in suspected cases catheterization 
of the ureters should be resorted to, which may possibly elicit some 
information of value. 

4. In mild cases of cystitis pus may be altogether absent, while in 
the more severe forms its presence is constant. In cystitis the 
largest amounts of pus referable to disease of the urinary organs 
are observed, exceeded only in those rare conditions in which a neigh- 
boring abscess has suddenly discharged itself through the urinary 
passages. 

As the urine in cystitis is usually alkaline, and always so in 
the more severe forms, the alkalinity being due to ammoniacal fer- 
mentation, it may happen, owing to the disintegrating action of am- 
monium carbonate upon the pus-corpuscles, that these may not even 
be demonstrable with the microscope, and that a gelatinous mucoid 
sediment appears instead, which escapes from the vessel en masse 
when the urine is poured out. Vitali's test for pus (referred to on 
p. 437) should be employed in such cases. 

5. In urethritis pus may be eliminated in the urine in consider- 
able amounts. The source of the pus is recognized by the fact 
that a drop may be manually expressed from the urethra, particu- 
larly in the morning upon awaking. Mucoid gonorrhoea! threads, 
which are largely composed of pus-corpuscles, will almost always 
be detected in the urine in such cases, the so-called " Tripperfaden " 
of the Germans. In order to distinguish between a simple ure- 
thritis and a urethritis complicated with cystitis, the urine should 
be obtained in two portions and allowed to settle. In cases of 
simple urethritis affecting the anterior portion of the urethra the 
first specimen will be cloudy, while the second one is clear. If 
the urethritis, however, has extended to the neck of the bladder, 
in the absence of a cystitis, while the first portion will, of course, 
be cloudy, the second portion may present a variable appearance, 
being clear at times and cloudy at others. This phenomenon is 
explained by the fact that a portion of the pus contained in the 
posterior portion of the urethra has found its way into the bladder. 
A cystitis may, however, be excluded by the acid reaction of the 
second specimen, and the fact that the latter is never so cloudy 
as the first ; while in cases of urethritis complicated with a puru- 
lent cystitis the second portion contains at least as much pus as 
the first, and usually more, owing to the pus, which is heavier than 
the urine, falling to the floor of the bladder, in which case also the 



440 CLINICAL DIAGNOSIS. 

last drops passed will often be found to be pure pus. The reactiou 
of the urine, moreover, will then generally be alkaline. 

6. A sudden elimination of large quantities of pus in a urine which 
up to that time has presented a normal or nearly normal appear- 
ance may almost always be referred to the rupture of a neighboring 
abscess into the urinary passages. Exceptions to this rule have been 
noted in rare instances in which large amounts of pus suddenly 
appeared, the origin of which could not be demonstrated upon post- 
mortem investigation. Whether such a phenomenon, as v. Jaksch 
suggests, is dependent upon " unusual conditions favoring diapede- 
sis " remains an open question. 

Red Blood-corpuscles. The presence of red blood-corpuscles 
in the urine, constituting the condition usually spoken of as hcema- 
turia, is observed only in pathologic conditions, and is, in contra- 
distinction to hemoglobinuria (which see), a very common occur- 
rence. 

Urine containing blood-corpuscles in notable numbers presents a 
color which may vary from a bright red to a dark brown, verging 
upon black. Upon standing a sediment of a corresponding color is 
obtained in which distinct coagula of variable size are at times seen. 

If the urine should contain but a small number of red corpuscles, 
however, no deviation from its normal appearance will be noted, and 
the diagnosis of haematuria can then only be made with the micro- 
scope, which should be employed in every case. The appearance of the 
red corpuscles varies greatly, being influenced especially by the length 
of time during which they have been exposed to the action of the urine. 
In cases of hematuria of urethral or vesical origin it will be found 
that they have mostly retained their normal appearance fairly well, 
or have become crenated, when they may be recognized without 
difficulty. Others, however, will probably also be seen at the same 
time which are no longer biconcave, but which have become spherical 
or shrunken, presenting an irregular outline. In cases, on the other 
hand, in which the corpuscles have remained in the urine for a 
longer time, as, especially, in hematuria of renal origin, the inex- 
perienced will frequently be puzzled by the presence of small bodies 
of the size of red corpuscles, or somewhat smaller, which are entirely 
devoid of coloring-matter, and merely appear as faint, transparent 
rings, often presenting a double contour, and in which no nucleus can 
be discovered. These formations are red blood-corpuscles, from which 
the haemoglobin has been dissolved. They are usually spoken of as 



THE URINE. 441 

blood-shadows. Chemical tests are rarely necessary, but may be 
employed if any doubt should arise (see p. 366). 

Clinically it is, of course, all important to determine the source of 
the blood. This may at times be accomplished without much diffi- 
culty by a urinary examination, but at other times may be almost 
impossible, when the clinical symptoms and physical signs must be 
taken into consideration. 

1. Hematuria of urethral origin, due to urethritis, traumatism in- 
cident to catheterization, for example, is a common event, and readily 
diagnosed, as in such cases blood either escapes of its own accord 
from the urethra or may be squeezed out manually. The last por- 
tions of the urine voided, moreover, will always be found free from 
blood, unless indeed the latter is referable to disease of the neck of 
the bladder, when the blood appears only toward the end of mictu- 
rition, or then at least more markedly than in the beginning. 

2. The diagnosis of vesical hematuria is not always easily made. 
It should be remembered, however, that here the blood-corpuscles 
present a normal appearance, as has been mentioned, unless am- 
moniacal fermentation is occurring in the bladder, in which case 
blood-shadow T s are seen in large numbers. The blood, moreover, is 
less intimately mixed with the urine than in cases of renal hematuria, 
so that the corpuscles rapidly settle down after the urine has been 
passed. Blood-clots of an irregular form and considerable dimen- 
sions can only be of vesical origin. A careful examination into the 
presence of any other morphologic constituents which may be ob- 
served in urinary sediments, considered in conjunction with the 
clinical symptoms, will usually lead to a correct diagnosis so far as 
the seat of the hemorrhage is concerned. Hematuria of vesical 
origin may be due to numerous causes, among which may be men- 
tioned diphtheritic cystitis, ulcers of the bladder caused by calculi 
and carcinoma, traumatism, the presence of parasites, and, more 
rarely, rupture of varicose veins in the bladder. In determining 
the causes of the hemorrhage in a given case more reliance should be 
placed upon the clinical history than upon the urinary examination. 

3. In hematuria of ureteral origin characteristic blood-coagula 
corresponding in diameter and form to the ureters are occasionally 
seen. Their presence, however, does not necessarily indicate that 
the blood has come from the ureters, and more frequently the hemor- 
rhage will, in all probability, be found to be due to disease of the 
pelvis of the kidney. 



442 CLINICAL DIAGNOSIS. 

4. The diagnosis of hemorrhage into the pelvis of the kidney must 
be based upon the clinical symptoms taken iu conjunction with the 
results 01 a urinary examination. In doubtful cases recourse should 
be had to catheterization of the ureters, when a unilateral hematuria 
may in the majority of cases be regarded as referable to this source. 

5. Hematuria of renal origin proper is of common occurrence, 
and may be dependent upon numerous causes, such as a simple 
hyperaemic condition of the organs, acute nephritis, in which the 
passage of smoky-looking urine containing blood-corpuscles, usually 
in large numbers, is quite a constant symptom, and chronic nephritis, 
in which their number may be taken to indicate the intensity of the 
morbid process. Hematuria may also be due to renal abscess, 
nephrophthisis, renal carcinoma, and, in rare instances, to aneurism 
and embolism of the renal artery, thrombosis of the renal vein, etc. 
In the malignant forms of the acute infectious diseases, such as 
smallpox, yellow fever, malaria, etc., in scurvy, haemophilia, pur- 
pura, in leukaemia, and filariasis, renal hematuria is likewise a 
common event. It is also observed in cases of poisoning with tur- 
pentine, carbolic acid, cantharides, etc. 

Hematuria of renal origin is usually recognized without much 
difficulty, as in such cases tube-casts, bearing red blood-corpuscles, 
and at times apparently consisting of these altogether, as well as 
numbers of renal epithelial cells, will usually be found upon careful 
examination. The blood, moreover, is intimately mixed with the 
urine, and the individual corpuscles have mostly lost their haarno- 
globiu and appear as mere shadows. The clinical history should, of 
course, always be taken into consideration, and especially in deter- 
mining the primary cause of the hemorrhage. 

Urine containing red blood-corpuscles is always albuminous, so 
that it may be difficult under certain circumstances to decide whether 
in a given case the albumin found is solely referable to the presence 
of blood, or whether the hematuria is complicated with an albumi- 
nuria per se. Frequently it is possible to arrive at some conclusion 
by comparing the amount of albumin with the number of red cor- 
puscles, the presence of a large amount of the former in the presence 
of only a small number of the latter indicating that the albumin is 
not altogether owing to the blood. At other times it is impossible 
to gain information in this manner, when the only expedient left is 
to determine the quantity of albumin and of iron separately, and to 
ascertain whether the amount of iron found is sufficient to combine 



THE URINE. 443 

with that of the albumin. As a general rule, however, the presence 

of serum-albumin, aside from that contained in the blood of the 
urine, may be inferred whenever tube-casts are present, although the 
amount can only be estimated approximately in this manner. 

Tube-casts. In various pathologic conditions, and it is claimed 
even in health, curious formations are seen in the urine, which rep- 
resent moulds of different portions of the uriniferous tubules. To 
these the term tube-casts or urinary cylinders has been applied, and 
it may be said that there is hardly a subject of greater importance in 
urinary analysis, from a clinical point of view, than that of cylin- 
droma, but it must also be admitted that notwithstanding numerous 
investigations our knowledge of their nature and mode of formation 
is still defective, and the same may be said of their clinical signifi- 
cance. The term " tube-cast," however, is not altogether appro- 
priate, and it is only applicable to one great division of such forma- 
tions, i.e., to those consisting of a uniform, transparent, gelatinous 
matrix to which other elements, such as epithelial cells, red blood- 
corpuscles, leucocytes, and salts in a crystalline or amorphous 
form, may accidentally have become attached — the tube-casts proper. 

From these what may be termed " pseudo-casts " must be sharply 
separated, a pseudo-cast being characterized essentially by the absence 
of a uniform matrix. Closely related apparently to the true casts 
are the so-called cylindroids, baud-like formations which somewhat 
resemble the former in appearance, and like these may carry various 
morphologic elements, as well as salts. It is thus necessary to 
distinguish between true casts, pseudo-casts, and cylindroids. Of 
these the true casts are by far the most important and the most 
common. They may be divided into hyaline and waxy casts, the 
two forms being readily differentiated by the fact that the former 
readily dissolve in acetic acid, while the waxy casts are either not 
affected at all by this reagent, or, if so, at least not as rapidly. The 
latter, moreover, are more strongly refractive, to which property 
their waxy appearance is owing ; their color is slightly yellow or 
yellowish-gray, while the hyaline casts are colorless and usually 
very pale and transparent. 

Before giving a detailed description of these various forms it may 
not be out of place to consider briefly the mode of examination that 
should be employed. 

As tube-casts readily undergo disintegration within a compara- 
tively short time in urines containing bacteria even in moderate num- 



444 CLINICAL DIAGNOSIS. 

bers, a microscopic examination should be made as soon as possible 
after the urine has been voided, i.e., as soon as a sufficient sediment 
has formed. The examination should never be delayed longer than 
twelve hours, unless some antiseptic substance has been added. For 
this purpose chloroform-water (5-7.5 grammes pro liter) is the 
most convenient according to Salkowski, of which 20 to 30 c.c. 
should be used for every 100 c.c. of urine. The use of the centrif- 
ugal machine is, of course, best of all, as a sediment sufficient for 
microscopic purposes may be obtained in a few minutes. In the 
text-books on urinary analysis mention is usually made of the 
difficulty attending the search for hyaline casts, owing to their trans- 
parency, and the advice is usually given to color the preparation with 
a drop of a dilute solution nf iodo-potassic iodide, or of some other 
staining reagent, such as gentian-violet, picrocarrain, methylene- blue, 
etc., or even osmic acid. In the case of the inexperienced it is possible 
that such a procedure may at times be of value, but, as a rule, 
it may be doubted whether a student who has been unable to find 
tube casts, if the procedure which has been described above be em- 
ployed, i.e., careful examination, without a cover-glass and with a 
low power, of a drop of the sediment carefully spread over a slide, 
will be materially aided by the use of stains. With a high power 
of the microscope, it is true that tube-casts may be overlooked again 
and again, not only by the student, but also by those familiar with 
clinical microscopy : a high 'power should, as a rule, only be em- 
ployed to study details of structure. 

True casts. 1. Hyaline casts. (Fig. 113.) Upon careful examina- 
tion it will be seen that with rare exceptions the matrix of hyaline 
casts is not altogether homogeneous, as small granules may almost 
always be detected imbedded in or adhering to the matrix. As 
these granules may occur in greater or less numbers, hyaline casts are 
spoken of as being finely granular (Fig. 114), coarsely granular, 
finely dotted, etc. Should true morphologic elements be detected, 
the casts are termed blood-casts, epithelial-casts (Fig. 115), or pus- 
casts. It W'Ould be better, however, to add the term hyaline in 
every instance, so as to distinguish them from pseudo-casts, which 
consist of these elements entirely, and lack a uniform matrix. It 
would thus be proper to speak of hyaline epithelial casts, hyaline 
blood-casts, etc., and to apply the collective term — compound- 
hyaline casts — to these various subvarieties. 

The true nature of these various forms can probably always be 



THE URINE. 
Fig. 118. 



445 






w 






,' . 



\ ^ ft 



tr°- 



-»:. 







k ! 








\«s 


VJ>'' 


\«\ 




■• .-• 


>s -" ;: ^iS:v,, 





Hyaline tube-casts. 
Fig. 114. 




Granular tube-casts. 
Fig. 115. 




446 



CLINICAL DIAGNOSIS. 



made out without much difficulty, and even iu those cases in which 
the h valine matrix is apparently concealed beneath cellular elements 
it will usually be possible upon closer observation to detect a fine 
boundary-line at some portion of the structure. Xot infrequently 
the end of the cast will be seen to be more or less distinctly hyaline. 
In others, again, a hyaline zone may be observed to run along the 
sides of a central organized thread, so to speak, this being frequently 
seeu in specimens which are very broad and long. Should any 
doubt, however, arise, a drop of acetic acid is added to a drop of 
the sediment on the slide ; the acid dissolves the hyaline matrix, the 
organized constituents are set free, and the differential diagnosis be- 
tween a pseudo-cast and a compound hyaline cast is thus readily 
established. 

Fig. 116. 




a. Fatty casts, b and c. Blood-easts, d. Free fatty molecules. (Roberts.; 



The length of hyaline casts may vary greatly. It may scarcely 
exceed the breadth on the one hand, while on the other, although 
rarely, it may pass through the entire microscopic field. In breadth 
they vary between 0.01 and 0.05 mm. As a rule the breadth of a 
cast is uniform throughout its entire length, but specimens are not 
infrequently observed in which one end tapers off considerably and 
presents a spirally twisted appearance. This may go on to such an 
extent that the entire cast becomes transversely striated. It is gener- 
ally supposed that this results from the adhesion of one end of the 
cast to the walls of a tubule the lumen of which it does not fill, the 



the urim:. 



117 



Fig. 117. 



other, or free end, becoming twisted in the downward course. A 
dichotomoua branching of one end is also at times observed in very 
broad hyaline specimens. 

" Fatty globules are found upon the surface of granular casts 
(Fig. 116), but they also form by themselves short, strongly refrac- 
tive easts, which are often beset all over with needles of fatty crystals. 
These, however, are not composed exclusively of fat, but probably 
to some extent of lime and maguesia salts of the higher fatty acids 
and allied compounds, for they are not all soluble in ether. They 
have their origin doubtless in fatty degeneration of the renal epi- 
thelium " (v. Jaksch). 

Granules of melanin, indigo, and altered blood-pigment may also 
at times be observed in casts ; Riedel regards the occurrence of 
casts colored a dark brown as pathognomonic 
of fractures. 

2. The waxy casts (Fig. 117) may be di- 
vided into two groups — true waxy casts and 
amyloid casts ; but as the latter are not 
necessarily indicative of the existence of 
amyloid degeneration of the kidneys, such a 
classification is at the present time at least of 
only theoretical interest. They are readily 
distinguished from the hyaline casts by the 
characteristics mentioned above; i.e., their 
higher degree of refraction, their yellow or 
yellowish-gray color, and the fact that they 
are either not attacked at all by acetic acid 
or only very gradually. As a rule, only 
small fragments are found, but these are 
broader and stouter than the stoutest hyaline 
casts. Waxy casts may also contain cellular 
elements, crystals, and amorphous mineral D 
matter ; but, as a rule, such compound casts a. with a coating of urates. 

e ,ii l • ,i b. Waxy cast covered with 

are not so frequently observed as in the case crystals of oxalate of lime . 
of the hyaline variety. From the latter c - Fragments of waxy casts. 
they differ furthermore in frequently present- 
ing a cloudy appearance, which in some cases is undoubtedly 
due to the presence of innumerable bacteria, and it has even been 
suggested that these may be directly concerned in their produc- 
tion. 





448 CLINICAL DIAGNOSIS. 

As has just been stated, some waxy casts give the amyloid reac- 
tion ; i.e., they assume a mahogany color when treated with a dilute 
solution of iodo-potassic iodide, which turns to a dirty violet upon 
the addition of dilute sulphuric acid. It should be remembered, 
however, that this reaction in casts does not necessarily indicate the 
existence of amyloid disease of the kidneys, as the reaction may be 
absent on the one hand in this condition, and present on the other 
where amyloid degeneration does not exist. This curious phenome- 
non is usually explained by assuming that such casts have remained 
in the uriniferous tubules for a long time, and have there undergone 
certain chemical changes analogous to the so-called " amyloid 
metamorphosis " of old precipitates of fibrin, and it is indeed possi- 
ble that waxy casts are originally hyaline. Frerichs has pointed out 
that fibrin which has remained in the uriniferous tubules for a long 
time becomes denser and yellowish in appearance, which would ex- 
plain the fact that these casts are only with difficulty attacked by 
acetic acid. 

Before leaving this subject it should be stated that " cast-like " 
formations, which consist entirely of amorphous urates, are not in- 
frequently encountered in urines, and according to Leube they may 
be obtained from any urine, if this be concentrated in the vacuum 
at a temperature of 37° to 39° C. Students frequently regard 
such formations as coarsely granular casts, an error which may be 
guarded against if the characteristics of hyaline casts set forth above 
be borne in mind. 

Bacteria (in cases of infectious pyelo-nephritis), hsematoidin, and 
granular detritus frequently occur grouped in a cast-like manuer, the 
nature of which may, however, be readily ascertained, as in the case 
of the so-called urate casts just referred to. 

Pseudo-casts may consist of epithelial cells or blood-corpuscles 
and fibrin, and are rarely seen in urinary sediments. The epithe- 
lial pseudo-casts are probably only seen in cases of desquamative 
nephritis, and, in contradistinction to the true casts, are hollow, 
the epithelium of the uriniferous tubules being thrown off en masse. 
Blood-casts (Fig. 116) consist of fibrin, within the meshes of which 
red corpuscles, presenting either a normal appearance or occurring 
as mere shadows, owing to the fact that their haemoglobin has been 
dissolved out, will generally be found. They are found whenever 
extensive hemorrhage has taken place in the renal parenchyma, and 
are far more frequently seen than the epithelial pseudo-casts. Hya- 



THE URINE. 



449 



line casts are probably always met with in urinary sediments in 
which pseudo-casts are found, and may be readily distinguished Irom 
the latter, even when beset with numerous epithelial cells or red cor- 
puscles (see above). 

Cijlindroids (Fig. 118) somewhat resemble hyaline tube-casts in 
general appearance, but differ from these in being much larger and 



Fig. US. 



Fig. 119. 




/ // 



a and b. Cylindroids from the urine in 
congested kidney, (v. Jaksch.) 



Mucous cylinders. 



band-like. Like the tube-casts, they present a uniform breadth, and 
are often beset with crystals and cellular elements, such as leucocytes, 
red corpuscles, and epithelial cells. They are easily dissolved by 

29 



450 CLINICAL DIAGNOSIS. 

acetic acid, thus differing from the mucous cylinders or pseudo- cyl- 
inders (Fig. 119), which may be observed in any urine containing 
mucus in abundance; the latter probably never contain morpho- 
logic or mineral constituents, and are never of the same breadth 
throughout their length. The cylindroids proper are undoubtedly 
of renal origin and closely related to the true casts ; formations are 
indeed not at all infrequently seen in which a tube-cast terminates 
in a cylindroid at one or both ends (see Fig. 113). 

Formation of tube-casts. Several hypotheses have been advanced 
to explain the formation of tube-casts — reference is here only had to 
true casts, and not to the pseudo-casts, the origin of which is suffi- 
ciently obvious — and until recently it appeared to be quite generally 
accepted that these consisted of coagulated albumin which had 
transuded into the tubules ; according to this view a cylindruria 
would always be indicative of the existence of albuminuria. In 
Neubauer and VogePs latest edition (ninth) it is stated that (i as to the 
significance of tube-casts it must be remembered that these, according 
to our present knowledge, consist of albumin, which coagulates under 
the influence of the acid reaction of the urine in the renal paren- 
chyma in a peculiar hyaline manner. They merely represent a 
solidified portion of the albumin held in solution by the urine ; their 
elimination essentially indicates the existence of an albuminuria." 

More recently, however, probably owing to the reported absence 
of albumin in certain cases of cylindruria, it has been suggested that 
tube-casts are the product of a faulty metamorphosis, or of inflam- 
matory irritation of the renal epithelium, and that a secretion from 
these cells or a disintegration of their protoplasm occurs, resulting 
in the formation of cylindroids or true casts. As far as the exist- 
ence of a cylindruria sine albuminuria is concerned, the author must 
confess that he is very skeptical as to the actual occurrence of such a 
condition, and he fully agrees with Neubauer and Vogel when they 
state that " whenever the number of tube-casts is minimal the cor- 
responding amount of albumin may be so insignificant that it may 
not be demonstrable by means of the ordinary, coarser tests." In 
several thousand examinations a case of cylindruria sine albuminuria 
has never been observed. It is difficult, moreover, to imagine that 
an elimination of blood-casts and others, which, according to Kossler, 
are " frequently" encountered in urines, can take place in the ab- 
sence of a coincident elimination of albumin, as is claimed by him, 
and until further and more convincing evidence is offered in favor 



THE URINE. 451 

of a cellular origin of tube-casts, it may be better to be conservative 
and to regard cvlindruria as equivalent to albuminuria. 

Clinical significance of tube-casts. Formerly the occurrence of 
tube-casts in the urine was regarded as indicating the existence of 
nephritis. This view has been abandoned, however, for the same 
reasons which led to the rejection of the theory that albuminuria 
invariably indicates Bright' s disease (see above). 

The statement is frequently made in text-books that tube-casts 
may occur in the urine of perfectly healthy individuals following 
severe muscular exercise, cold baths, etc. ; in short, all stimuli which 
may cause the appearance of albumin in apparently normal indi- 
viduals. It has been indicated elsewhere (see Functional Albu- 
minuria), however, that such stimuli should not be regarded as 
" physiologic" stimuli in every instance, and the presence of tube- 
casts in the urine similarly should be regarded as a pathologic event. 

It will not be necessary in this connection to enumerate the vari- 
ous pathologic conditions in which cyliudruria is observed, these 
being the same as those which give rise to albuminuria ; and just as 
a nephrangiogenic albuminuria is more frequently observed than a 
nephritidogenic albuminuria, so also is the presence of tube-casts in 
the urine more frequently due to circulatory disturbances in the 
kidneys than to true nephritis. In every case in which tube-casts 
occur in the urine it may be assumed that the accompanying albumi- 
nuria is, to a certain extent at least, of renal origin. 

While the existence of cylindruria is not necessarily associated 
with definite pathologic alterations affecting the renal parenchyma, 
this statement should be restricted to the occurrence of purely hya- 
line casts when present only in small numbers. A few renal epi- 
thelial cells may be found at the same time, occurring either free in 
the urine or adhering to the casts, but never presenting an atrophic 
or otherwise altered appearance in the absence of definite renal 
lesions. The presence of compound hyaline and coarsely granular 
casts, as well as of waxy and amyloid casts, on the other hand, may 
probably always be regarded as indicating definite changes in struc- 
ture, so that, so far as the diagnosis of nephritis is concerned, a micro- 
scopic examination of the urine will furnish information far more 
valuable than the simple demonstration of albumin. 

Hyaline casts are those most usually seen — reference is here had 
only to the purely hyaline or, at least, but faintly granular form — 
and are found in all conditions in which albuminuria occurs. When 



452 CLINICAL DIAGNOSIS. 

present in only small numbers, and particularly when occurriug but 
temporarily in the urine, it may be assumed, in the absence of other 
symptoms pointing to renal disease, that we are dealing with a mild 
circulatory disturbance in the kidueys. Renal epithelial cells will 
be altogether absent, or, if present, they will occur in only small 
numbers and present no special alterations in structure. The 
albuminuria at the same time will only be trifling. If, however, 
hyaline casts be present in large numbers continuously, and if the 
amount of albumin exceed a trace, the existence of a nephritis may 
usually be inferred. In such cases granular casts and compound 
hyaline casts, particularly the former, will usually also be found, if 
the nephritis be chronic, while in the acute form the hyaline type 
will prevail. Should blood-casts be present at the same time, the 
probabilities are that we are dealing with an acute nephritis, or an 
acute exacerbation of a chronic process, in which latter case, how- 
ever, coarsely granular casts will also be present in large numbers. 

Waxy casts always indicate a chronic or, at least, a subacute pro- 
cess. The fatty casts described by Knoll and v. Jaksch u are most 
commonly associated with subacute or chronic inflammations of the 
kidney of protracted course, with a tendency to fatty degeneration of 
the renal tissues. Post-mortem examination has shown that they 
form most frequently in cases of large white kidney. In some cases 
in which they were present, however, the organ was found to be 
more or less contracted ; but when this was so, it was invariably far 
advanced in fatty degeneration." 

It has been stated above that from a careful examination of the 
renal epithelial cells it is often possible to determine whether an in- 
flammatory process affecting the kidneys is at the same time com- 
plicated with degenerative changes. As a matter of fact, the cells 
which are found on the tube-casts under such conditions no longer 
present a normal appearance, but have become shrunken and atro- 
phic, and in cases of fatty degeneration of the kidneys are seen to be 
studded with fatty granules. Epithelial casts, in the absence of dis- 
tinct changes affecting the renal parenchyma, are probably never seen. 

The occurrence of pus-casts presupposes the existence of suppur- 
ative inflammation in the kidneys, while the presence of only a small 
number of leucocytes on hyaline casts may be observed in the ordi- 
nary forms of nephritis and particularly in the acute form. 

The pathologic significance of the so-called amyloid casts and 
pseudo-casts has already been considered. 



THE URINE. 



453 



Cylindroids are present whenever hyaline casts are seen in the 
urine, and have essentially the same import. They are said to occur 
most frequently in the urine of children. 

So far as the constancy with which tube-casts occur in the urine 
in nephritis is concerned, it is well known that in the chronic inter- 
stitial form of the disease they, as well as albumin, are frequently ab- 
sent for a long time, so that it may only be possible to make the 
diagnosis from the cliuical history and the physical signs. It is a 
well-known fact, moreover, that pathologic alterations of the kidneys, 
particularly in men beyond middle-age, are observed again and again 
in the post-mortem-room, where a previous examination of the urine 
showed no evidence of the existence of renal disease. In the acute 
and subacute forms of nephritis as well as in the ordinary parenchy- 
matous form, tube-casts are probably always found, and it would 
further appear that acute circulatory disturbances affecting the renal 
parenchyma quite constantly lead not only to albuminuria, but also 
to cylindruria. 

Spermatozoa. Spermatozoa, for a description of which the 
reader is referred to the chapter on Semen, are frequently observed 

Fig. 120. 




Human spermatozoa. 



in the urines of perfectly healthy adults, and are quite constantly 
met with in the first urine passed after coitus or pollutions, when 
their presence is, of course, of no significance. (Fig. 120.) Such 
urines are always cloudy, but it is impossible to recognize the source 
of the turbidity by simple inspection. 



454 CLINICAL DIAGNOSIS. 

A sediment composed of phosphates is popularly regarded as 
being due to semen, and no doubt every physician has seen patients — 
usually sexual neurasthenics to a greater or less degree — who have 
been greatly alarmed at finding a white deposit in the chamber, and 
who imagined themselves "sufferers from loss of manhood." The 
microscope is necessary in every case to determine the presence of 
spermatozoa. 

In females semen is found in the urine whenever the external 
genitals have been polluted during or after coitus as well as in the 
exceptional cases in which connection has been effected by the urethra. 
From a medico-legal standpoint the discovery of spermatozoa in the 
urine of women may be of the greatest importance, but otherwise is 
without significance. 

In pathologic conditions spermatozoa are not infrequently found 
in the urine. In cases of severe constipation, owing to the irrita- 
tive action of the hard scybala upon the seminal vesicles, a partial 
evacuation of semen may occur, which may or may not be accom- 
panied by a certain degree of sexual excitation. Horowitz has pointed 
out that a discharge of semen may be noted in cases of periurethral 
abscess with perforation into the ejaculatory ducts, giving rise to 
spe?matocystitis, the condition being due to a tight stricture of the 
urethra with dilatation beyond the constricted portion. The author 
observed a case of cystitis in which spermatozoa could almost always 
be detected in the urine. An operation here revealed a very tight 
stricture of the urethra and a dilatation behind the constriction, which 
was at first mistaken for the bladder, and in which the constant 
elimination of semen apparently was owing to the irritating action of 
the ammoniacal urine. It should be noted that in this case, as well 
as in those in which semen is frequently passed during the act of 
defecation in the absence of sexual excitement, no deleterious effects 
referable to such loss were noted. In the urine voided during or 
after epileptic and, more rarely, hystero-epileptic seizures, sperma- 
tozoa may be found in the urine. Such an event is undoubtedly 
due to muscular spasm, and is identical in origin with the emis- 
sion of semen observed so frequently after death, during strangula- 
tion, etc. 

In certain spinal diseases semen may be found in the urine, and 
Fiirbringer relates a most interesting case in which, following frac- 
ture and dislocation of the vertebral column, with partial destruction 
of the middle dorsal cord, spermatorrhoea associated with partial 



THE URINE. 455 

erection occurred thirty hours later, ana continued until death, which 
took place after three days. 

Most important, however, is the loss of semen noted in cases ol 
true spermatorrhoea due to venereal excesses, or masturbation, when 
spermatozoa may be found in the urine almost constantly, and the 
diagnosis indeed will often be dependent upon such an observation. 

As far as the question of sterility in the male is concerned, reliance 
should not be placed upon an examination of the urine, but the 
semen should be separately obtained as soon as possible after coitus 
and examined as indicated elsewhere (see p. 477). 

Parasites. Vegetable parasites. The vegetable parasites which 
may be found in the urine belong to the class of fungi, and may be 
divided into moulds, yeast, and fission-fungi. It is well known that 
the latter, wdiich are of especial interest, occur in every old urine in 
enormous numbers. They are, however, only accidentally present, 
and must hence be considered as foreign matter. It is important to 
note that urine obtained in such a manner as to guard against acci- 

FlG. 121. 



Micrococcus urea. 

deutal contamination is sterile and free from bacteria. It has been 
pointed out that ammoniacal fermentation is due to the action of 
certain bacteria, especially the micrococcus ureoz. This organism is 
therefore found in every urine in which fermentation has begun, and 
is readily recognized, occurring in almost pure culture upon the sur- 
face of the urine, mostly in the form of characteristic chains. (Fig. 
121.) The individual coccus is colorless, and so large that it may 
be mistaken by the student for a blood-shadow. It is a common 
error to infer from the occurrence of ammoniacal decomposition very 
soon after micturition that this process has already begun in the 
bladder, indicating the existence of cystitis. It should be remem- 
bered that urines may undergo fermentation, particularly in warm 
weather, shortly after having been voided, and especially if the vessel 
employed is not absolutely clean and the urine has been allowed to 
stand exposed to the air. The diagnosis of ammoniacal fermentation 



456 CLINICAL DIAGNOSIS. 

in the bladder should hence only be made when the presence of am- 
monia can be demonstrated in the urine immediately upon being 
voided. Other bacteria are also found in every fermenting urine, 
but are of no special interest. 

The urinary sarcina which is at times met with is larger than that 
found in the gastric contents, but otherwise presents the same ap- 
pearance. 

Yeast-cells in large numbers are onlv seen in urines containing 
sugar. Whenever a chemical examination has not been made their 
demonstration will be of importance, as possibly suggesting the ex- 
istence of diabetes. 

Moulds are usually seen in old diabetic urines after alcoholic fer- 
mentation has taken place, but may also occur, though far less fre- 
quently, upon the surface of putrid urines that have contained no 
sugar. 

While the occurrence of these various forms of fungi in old urines 
is practically without clinical significance, the elimination of bacteria 
through the kidneys, which may be observed in all of the acute in- 
fectious diseases, is a matter of great significance, and particularly so 
as it has been demonstrated that, as a general rule, those organisms 
are eliminated which have caused the morbid process. Their pres- 
ence, moreover, may be regarded as indicating the existence of some 
definite alteration of the renal parenchyma, although this need not 
necessarily be in the sense of a nephritis, which latter is referable to 
a ptomaine intoxication rather than to the action of the bacteria 
themselves. An infectious nephritis, however, is probably always 
associated with an abundant elimination of bacteria in the urine, and 
v. Jaksch was able to observe that in erysipelas the bacteriuria and 
nephritis disappeared together with the cessation of the disease. Patho- 
genic organisms have been found in erysipelas, measles, scarlatina, 
relapsing fever, sepsis, typhoid fever, tuberculosis, etc. 

Unfortunately for practical purposes the diagnosis of the specific 
fevers can, however, only exceptionally be made by a bacteriologic 
examination of the urine. 

Clinically important is the fact that in tubercular disease affecting 
the urinary organs tubercle-bacilli may be found in the urine. The 
search for these, however, is frequently fruitless, and always tedious. 
In suspected cases, and particularly in those in which a careful exami- 
nation of the lungs has yielded negative results, an attempt should be 
made to find the organism in the urine. For this purpose the urine 



THE URINE. 457 

must be obtained with the catheter, to avoid an admixture with the 
urine of smegma-bacilli, which closely resemble the tubercle-bacilli 

morphologically, and can be distinguished from the latter only with 
difficulty, as they stain in the same manner. The urine is set aside 
until sufficient sediment has been obtained, which is then examined as 
described in the chapter on Sputum. Very frequently it is necessary 
to prepare a large number ol cover-glass specimens, but, as stated 
above, even then the search may be without result, notwithstanding 
the existence of a tubercular lesion. In such an event it will be best 
to inject a few drops of the sediment into the anterior chamber of the 
eye of a rabbit, the urine being obtained under bacteriologic precau- 
tions, and to watch for the development of miliary tubercles in the 
iris. Isolated tubercle-bacilli have also been found in the urine in 
cases of acute miliary tuberculosis, when their search is still more 
tedious ; and in doubtful cases it will certainly be best to resort to 
the animal experiment at once. 



Fig. 122. 



® 








The gonococcus of Xeisser. 

In this connection it may not be out of place to refer to the gono- 
coccus of Neisser, which may now be definitely regarded as being 
pathognomonic of gonorrhoeal infection. The organism (Fig. 122) 
occurs in the form of small oval or round granules, usually grouped 
in twos and fours, so as to resemble a German biscuit or the figure 
8, enclosed within pus-corpuscles and epithelial cells, although they 
may also occur free in the pus obtained from the urethra, in the 
vaginal discharge, or more rarely free in urinary sediments, as in 
cases of complicating prostatitis, periurethritis, etc. In making 
a diagnosis account should only be taken of specimens which are en- 



458 



CLINICAL DIAGNOSIS. 



Fig. 123. 



closed in cellular elements, as these alone can be regarded as charac- 
teristic. They are best stained with carbol-fuchsin. In cases of 
urethritis, it is only necessary to receive a small drop of the dis- 
charge upon a cover-glass, and to spread this out in as thin a layer as 
possible; after drying the preparation is passed through the flame of 
a Bunsen burner three or four times, and stained with a drop of the 
fuchsin solution without the application of heat. The excess of 
coloring- matter is removed by rinsing the specimen in water, when it 
is dried between layers of filter-paper, mounted in a drop of water, 
and examined with an oil-immersion lens, although with a little 
practice reliable results can also be obtained with a lower power. In 

conclusion, reference should be made 
of the occasional occurrence of true bac- 
teriuria of a non-pathogenic form. Such 
cases are very rare, and the diagnosis of 
idiopathic bacteriuria, as this form may 
be termed, should only be made if every 
possible outside source of the bacteria 
can be definitely excluded. According 
to Schottelius, this condition is not as- 
sociated with any pathologic lesion, 
More recently, however, cases of pye- 
litis have been recorded in which bac- 
teriuria existed, and in which the 
bacillus coli communis was obtained in 
pure culture. In such cases it would 
not be unnatural to look to the intes- 
tinal tract as the possible source of the 
bacteria, but it is curious to note that 
even in cases in which a most intense degree of intestinal putrefaction 
exists no bacteria are found in the urine. 

Urines containing bacteria in large numbers are always cloudy, 
and usually present an acid reaction ; unless a cystitis exists at the 
same time, attention will be directed to their presence by the fact 
that such specimens caunot be cleared by simple filtration. 

Animal parasites. Infusoria may at times be observed in old 
urines, but do not possess any special significance, v. Jaksch has 
thus noted bodies which were similar to the cercomonas found in the 
feces. Hassal described a special infusorium which he named Bodo 
urinarius, and Baelz observed numerous amcebse in the turbid urine 




A gonorrheal thread. 



THE URIXE. 459 

of a girl the subject of phthisis, which are described as being of 
larger size than the amceba coli. 

The ova of distoma haematobium and the filaria sanguinis hominis 
are at times found in the urine, their elimination being usually accom- 
panied by hematuria and chyluria. Echinococcus booklets and 
fragments of cysts may also be found, and in rare instances ascarides 
find their way into the urinary passages when a fistulous opening 
exists between the rectum and the bladder. 

Tumor-particles. Tumor-particles are so rarely seen in the 
urine that a more detailed account of their occurrence may be 
omitted, particularly so as it is seldom possible to base the diagnosis 
of tumor upon the presence of fragments in the urine, the clinical 
history and the physical signs being usually sufficient to reach a 
satisfactory diagnosis. 

Foreign Bodies. Among foreign bodies which may be found 
in the urine there may be mentioned particles of fat, fibres of silk, 
linen, and wool, etc. ; in short, material the presence of which is 
owing to the use of unclean vessels for the reception of the urine. 
Fecal matter may be passed per urethram ; such an occurrence, of 
course, always indicates the existence of some abnormal communica- 
tion between the bowel and the urinary passages, especially the 
bladder. Hair derived from a dermoid cyst may similarly be found. 
In hysteria foreign bodies of almost any kind may be shown the 
physician, as having been passed in the urine, such as hair, teeth, 
fish-bones wood, etc., and even snakes and frogs. The author had 
occasion to examine " gravel" " passed" from time to time by a 
hysterical patient in large amounts, " every attack being accom- 
panied by the most agonizing pains shooting down into the lower 
abdomen ;" the gravel upon examination proved to be mortar, ob- 
tained from the cellar of the patient's house. 



460 



CLINICAL DIAGNOSIS. 



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CHAPTER VIII. 

TRANSUDATES AND EXUDATES. 
DEFINITION. 

In health the so-called serous cavities of the body contain but 
very little fluid, and quantities sufficient for analytical purposes can 
normally only be obtained from the pericardial sac. In pathologic 
conditions, on the other hand, large accumulations of fluid may be 
observed not only in the serous cavities, but also in the areolar con- 
nective tissue, beneath the skin and between the muscles. When 
due to circulatory disturbances, a hydremic condition of the blood, 
or an insufficient elimination of water through the kidneys, such 
accumulations of fluid are spoken of as transudates, while the term 
exudates is applied to similar accumulations of inflammatory origin. 

Clinically, it is frequently difficult to distinguish between transu- 
dates and exudates, and large ovarian, pancreatic, and hydatid cysts, 
as well as cystic kidneys, may at times be mistaken for ascites. In 
such cases a careful chemical and microscopic examination of the 
fluid in question may be of decided value. Very frequently, more- 
over, it is possible only in this manner to determine the true nature 
of the disease, and the importance of freely using the trocar and the 
aspirating-needle in diagnosis cannot be too strongly advocated. 

TRANSUDATES. 

General Characteristics. 

Transudates are usually serous in character, when they present a 
light-straw color ; at times, however, owing to an admixture of 
blood, they present a reddish tinge, and are then spoken of as san- 
guineous ; in rare instances they are chylous. 

The Specific Gravity. 

The specific gravity varies somewhat according to the origin of the 
fluid, but is usually lower than that of serous exudates occurring iu 



462 



CLINICAL DIAGNOSIS. 



the same cavities, one of the most important points of difference be- 
tween the two kinds of fluid. Thus, in acute pleurisy the specific 
gravity of the exudate is usually higher than 1.020, and in chronic 
pleurisy, if an accumulation of pus exists at the same time, higher 
than 1.018, and even reaching 1.030. In transudates into the 
pleural cavity, on the other hand, referable to circulatory disturb- 
ances, for example, as in cases of hepatic cirrhosis or cardiac insuffi- 
ciency, the figures obtained are usually lower than 1.015. Transudates 
of peritoneal origin similarly present a specific gravity varying be- 
tween 1. 005 and 1 .0 1 5, while that of exudates frequently reaches 1 . 030. 

As the chemical composition, in so far as the mineral constituents 
and extractives are concerned, is practically the same in both classes 
of fluid, the difference in the specific gravity appears to be essentially 
due to the amount of albumin present, viz., serum-albumin and 
serum-globulin. It may be demonstrated, as a matter of fact, that 
exudates contain far more albumin than transudates, the amount 
varying between 4 and 6 per cent, in the former, as compared with 1 
and 2.5 per cent, in the latter. The largest amounts of albumin in 
transudates are found in those of pleural origin, while in oedema 
not more than 1 per cent, is usually present. 

In the table below, taken from Reuss, the relation between the 
percentage -amount of albumin and the corresponding specific gravity 
will be found. Reuss suggested the following formula for the pur- 
pose of determining the amount of albumin in transudates and exu- 
dates from the specific gravity : 

E = | (S — 1000) — 2.8, 



in which " E " indicates the percentage-amount of albumin and 
" S " the specific gravity, taken by means of an accurate urinometer : 



Specific gravity. 


Albumin. 


Specific gravity. 


1.008 . 


. 0.2 


1.019 . 


1.009 . 


. 0.6 


1.020 . 


1.010 . 


. 1.0 


1.021 . 


1.011 . 


. 1.3 


1.022 . 


1.012 . 


. 1.7 


1.023 . 


1.013 . 


. 2.1 


1.024 . 


1.014 . 


. 2.5 


1.025 . 


1.015 . 


. 2.8 


1.026 . 


1.016 . 


. 3.2 


1.027 . 


1.017 . 


. 3.6 


1.028 . 


1.018 . 


. 4.0 





Albumin. 

4.3 
4.7 
5.1 
d.o 
5.8 
6.2 
6.6 
7.0 
7.3 
7.7 



2.68 


0.37 


2.30 


0.84 


5.42 


2.70 


4.25 


3.36 



TRANSUDATES AND EXUDATES. 463 

The table below shows the percentage-amount of albumin obtained 
by Rnneberg in ascitic fluid under various pathologic conditions : 

Hydremia (Bright's disease, tuber- 
culosis, etc., with amyloid degene- Average. Maximum. Minimum, 
ration) 21 0.41 03 

Portal stasis (referable to hepatic 
cirrhosis or stenosis) . . . 0.97 

General venous stasis (referable to 
organic heart disease) . . . 1.67 

Carcinoma of the peritoneum (com- 
plicated with carcinoma of the 
stomach) 3.51 

Chronic peritonitis (one case compli- 
cated with heart disease) . . 3.71 

The fact, moreover, that transudates do not coagulate spontane- 
ously in the absence of blood may further serve to distinguish these 
from exudates, in which a coagulum is frequently observed after 
having stood for twenty-four hours. But not much reliance should 
be placed upon this point of difference, as exudates likewise do not 
always coagulate, and clotting of transudates in the presence of blood 
may already take place within the body. 



The Chemistry of Transudates. 

An idea of the chemical composition of the various forms of 
transudates may be formed from the following tables, taken from 
Hoppe-Seyler and Hammarsten, the figures corresponding to 1000 
parts by weight of fluid, and the specimens being taken from one 
individual : 



Water . 
Solids . 
Albumin 

Ethereal extract "j 
Alcoholic extract | 
Aqueous extract }■ 
Inorganic salts 
Errors of analysis J 



Pleura. 




Peritoneum. 


03dema of 
the feet. 


957.59 




967.68 


982.17 


42.41 




32.32 


17.83 


27.82 




16.11 


3.64 






5.27 


0.50 




1 
\ 

J 




3.71 


14.59 


10.94 


1.10 
9.00 






0.12 



464 CLINICAL DIAGNOSIS. 

Analysis of Hydrocele Fluid. 

Water 938.85 

Solids 61.15 

Fibrin (formed) 0.59 

Globulins 13.52 

Serum-albumin 35.94 

Ethereal extract 4.02 

Soluble salts 8.60 

Insoluble salts 0.66 

Sodium chloride 6.19 

Sodium oxide 1.09 

Sugar and uric acid in small amounts are also, as a rule, found 
in transudates, and in one case of hepatic cirrhosis Moscatelli suc- 
ceeded in demonstrating the presence of allantoin. 

Microscopic Examination. 

Upon microscopic examination only a few isolated leucocytes and 
endothelial cells derived from the serous surfaces and undergoing 
fatty degeneration are seen. In cases in which the transudates have 
been confined for a long time in one of the serous cavities plates of 
cholesterin are frequently found. These appear to be especially 
abundant in hydrocele fluid. 

EXUDATES. 

Exudates may be serous, sero-fibrinous, sero-purulent, purulent, 
putrid, hemorrhagic, or chylous, terms which do not require further 
definition. 

The purulent, sero-purulent, and putrid forms are manifestly of 
inflammatory origin, while it may at times be difficult to decide the 
true nature of serous, sero-fibrinous, and sero-sanguineous fluids. In 
such cases the points of difference already described between transu- 
dates and exudates should be borne in mind, and will, when taken 
in conjunction with the physical signs and the clinical history, gener- 
ally lead to a correct diagnosis of the origin of the fluid. 

Serous Exudates. 

Serous exudates are clear, of a light-straw color, and present a 
specific gravity usually exceeding 1.008. After standing, a white 



TRANSUDA / /> 1 XD EXUDATES. 465 

fibrinous coagulum is generally Formed. Upon microscopic ex- 
amination some red corpuscles, which are probably referable to the 
puncture, polynuclear leucocytes, and endothelial cells undergoing 
fatty degeneration are found. Such exudates, as indicated, differ 
from the corresponding transudates in presenting a higher specific 
gravity, and in the fact that clotting is observed in transudates only 
in the presence of blood. Exudates, however, do not invariably 
coagulate, and too much importance should hence not be attached to 
this point. 

Hemorrhagic Exudates. 

Hemorrhagic exudates are essentially sero-fibrinous in character, 
the exact color depending upon the amount of blood-pigment present. 
Microscopic examination reveals the presence of a large number of 
red corpuscles, polynuclear leucocytes, and endothelial cells. Choles- 
terin-crystals may also at times be seen, though rarely in very large 
numbers. When numerous, attention is readily drawn to them, 
during the macroscopic examination of the fluid, by the peculiar 
glistening appearance of its surface. 

Tuberculosis. As hemorrhagic exudates are most commonly 
observed in cases of tuberculosis and of carcinoma of the lungs and 
pleura, the specimen should be carefully examined for the presence 
of tubercle-bacilli and cancer-cells. In every case it will be best 
to subject portions of the fluid to centrifugation and to examine 
the sediment thus obtained. Usually tubercle-bacilli are not found, 
even when tuberculosis of the pleura exists. If in such cases 
culture-experiments likewise prove negative and cancer-cells are not 
found, the diagnosis of probable tuberculosis will nevertheless be 
warrantable. 

Cancer. The diagnosis of cancer should be based upon the de- 
monstration of cancer-cells in the fluid. The physician, however, is 
warned not to mistake endothelial cells for cancer-cells. The diag- 
nosis should hence only be made when large epithelial cells of vari- 
able form, measuring at times 120// in diameter, are found in large 
numbers, especially when arranged in groups, unless, indeed, cancer- 
ous nodules presenting the characteristic alveolar structure are at 
once found. Quincke has drawn attention to the occurrence of large 
numbers of fat-droplets, which may attain a diameter of from 40 fx to 
50// in the fluid in cases of neoplasm. At times these fat-droplets 

30 



466 CLINICAL DIAGNOSIS. 

are so small and numerous as to give a chylous appearance to the 
exudate. At other times a similar appearance is due to the pres- 
ence of minute albuminous granules, which may be readily distin- 
guished from the former by their insolubility in ether. The occur- 
rence of numerous fatty-acid crystals arranged in groups should 
likewise be regarded as favoring the diagnosis of carcinoma. It is 
also claimed by Quincke that carcinoma probably exists if a 
marked glycogen reaction can be obtained in the endothelial cells. 
This test has already been described in the chapter on Blood (see 
p. 42). 

Of late Rieder has called attention to the occurrence of cells under- 
going division, their nuclei presenting essentially typical karyo- 
kinetic figures, which he regards as pathognomonic of carcinoma. 
Cover-slip preparations are prepared from the sediment, dried in the 
air, fixed by immersion for an hour in a mixture of equal parts of 
absolute alcohol and ether, and stained with a dilute solution of 
hematoxylin. 

Putrid Exudates. 

Putrid exudates are observed following the perforation of a gan- 
grenous focus or of a gastric or intestinal ulcer into one of the body- 
cavities. At other times they are encountered in cases of neoplasm 
and at times even without any apparent cause. The material ob- 
tained in such cases presents a brown or brownish-green color, and 
emits an odor which in itself indicates the character of the exudate. 
Microscopically cholesterin, hsematoidin, and fatty-acid crystals, as 
well as degenerating leucocytes, are found. In cases in which aspi- 
ration of a higher intercostal space reveals the presence of serous 
fluid, while putrid material is obtained at a lower point, the exist- 
ence of a subphrenic abscess should be suspected. In such cases a 
pure culture of the bacillus coli communis has been obtained. 
While the reaction of putrid exudates is usually alkaline, an acid 
reaction may be obtained in cases of perforation of a gastric ulcer. 
The sarcina ventriculi and sacchaiomyces may then be found. 

Pus. 

General Characteristics of Pus. If pus, which usually 
presents a color varying from yellowish -gray to greenish -yellow, be 
allowed to stand for some time, it will be seen that a liquid gradu- 



TRANSUDATES AND EXUDATES. 467 

ally appears at the top, increasing in amount, until it is finally pos- 
sible to distinguish two distinct layers, the one above the pus-serum, 
the other at the bottom the pus-corpuscles. Upon the number of 
the latter the consistence as well as the specific gravity of the pus is 
dependent. The latter may vary between 1.020 and 1.040, with 
an average of 1.031 to 1.033. Fresh pus has always an alkaline 
reaction, which may become neutral or slightly acid upon standing, 
owing to the development of free fatty acids, glycerine, phosphoric 
acid, and lactic acid. The color of pus-serum may be a light straw, 
a greenish, or a brownish-yellow. 

The Chemistry of Pus. The chemical composition of pus- 
serum and pus-corpuscles may be seen from the accompanying tables : 

Analysis of Pus-serum. 





I. 


II. 


Water 


. 913.7 


905.65 


Solids 


. 86.3 


94.35 


Albumins . 


. 63.23 


77.21 


Lecithin . 


1.50 


0.56 


Fat .... 


0.26 


0.29 


Cholesterin 


0.53 


0.87 


Alcoholic extract 


1.52 


0.73 


Aqueous extract 


. 11.53 


6.92 


Inorganic salts . 


7.73 


7.77 


Analysis of Pus-corpuscles. 






I. 


II. 


Albumins . 


. 137.62 




Nuclein . 


. 342.57 


f 673.69 
1 685.85 


Insoluble matter 


. 205.66 




Lecithin } 
Fat J 


. 143.83 


f 75.64 
1 75.00 


Cholesterin 


. 74.0 


72.83 


Cerebrin . 
Extractives 


. 51.99) 
. 44.33 J 


101.84 



Peptone is usually present, being derived from the corpuscles. 
Leucin and tyrosin are likewise frequently met with in the pus of 
old abscesses, and fatty acids, urea, sugar, glycogen, biliary pig- 
ments, and acids (in catarrhal jaundice), acetone, uric acid, several 
xanthin bases, cholesterin, etc., have occasionally been observed. 

Microscopic Examination of Pus. Leucocytes. If a drop 
of pus be examined with the microscope, it will be seen to contain 



468 CLINICAL DIAGNOSIS. 

innumerable leucocytes, the diameter of which varies from 8 a to 10 u, 
and which in fresh pus exhibit the characteristic amoeboid move- 
ments. It is curious to note that the so-called lymphocytes do not 
occur in pus, and even in the rare cases in which a predominance 
of this variety is met with in the blood, as in cases of lymphatic 
leukaemia, it will be observed that only the larger forms occur in 
the pus of abscesses which may have formed. While the leucocytes 
of fresh pus usually present a normal appearance, specimens may be 
seen in which amoeboid movements can no longer be observed, even 
upon the application of heat, and in which rounded vacuoles, filled 
with a clear liquid, and fatty granulations in moderate numbers 
may be seen. A predominance of such dead leucocytes usually in- 
dicates that the pus is old or has been formed in greatly debilitated 
subjects. 

Owing to a resorption of water taking place in accumulations of 
pus of long standing such material finally assumes a caseous aspect. 
in which the leucocytes will be seen to have greatly diminished in 
size, having at the same time assumed an angular, shrunken appear- 
ance ; in such cases it is hardly possible to demonstrate the presence 
of a nucleus even after the addition of acetic acid. 

It is noteworthy that in cases of hepatic abscess referable to the 
amoeba coli it is seldom possible to demonstrate any normal leuco- 
cytes, the pus upon microscopic examination consisting essentially of 
granular and fatty detritus, while in liver-abscesses due to other 
causes the leucocytes generally present a fairly normal appearance. 

Giant corpuscles. So-called giant pus-corpuscles, measuring at 
times from 30 ft to 40 fi in diameter, have been observed in abscesses 
of the gum, hypopyon, and in the contents of suppurating ovarian 
cysts, but do not appear to have any special significance. Upon 
careful examination these bodies will be seen to contain one oval 
nucleus, usually located excentrically within the cell, and from one 
to thirty or even forty pus-corpuscles. 

Detritus. Fatty and albuminous detritus in variable amount 
may be observed in every specimen of pus, increasing with the length 
of time that the latter has been confined within the body. The same 
holds good for the presence of free nuclei, which were formerly re- 
garded as young pus-corpuscles, but which have now been definitely 
recognized as originating during the disintegration of the corpuscles. 

Red corpuscles. Red-blood corpuscles in variable numbers are 
usually seen in every specimen, their appearance depending upon 



TIL I NJS f 'I>. I EBS - 1 SO EXUDATES. 469 

the length of time that they have been confined. Pns-corpiiscles may 
at times be seen to contain a red corpuscle. 

In doubtful cases it is always well to search carefully for the 
presence of tissue-elements, as it is only in this manner at times pos- 
sible to recoguize the true character of the morbid process. As the 
data of importance have already been detailed in other sections of this 
book (viz., Sputum and Urine), it will be unnecessary to recapitulate 
at this place. 

Pathogenic vegetable parasites. Among the pathogenic organisms 
encountered which are of especial interest from a clinical stand- 
point there may be mentioned the true pus-organisms, notably the 
staphylococcus pyogenes aureus and the streptococcus pyogenes ; 
furthermore, the tubercle-bacillus, the bacillus of syphilis, the actino- 
myces hominis, the bacillus of glanders, the bacilli of anthrax, lep- 
rosy, tetanus, influenza, and Frankel's pneumococcus, etc. The 
majority of these have already been described, and the reader is re- 
ferred for more detailed information to special works on bacteriology. 
In this connection it will be sufficient to state that, so far as pleural 
exudates are concerned, an absence of micro-organisms is usually in- 
dicative of tuberculosis, while the presence of Frankel's pneumo- 
coccus in exudates forming in the course of a pneumonia appears to 
be a favorable omen, as far as the origin of the pleurisy is con- 
cerned. 

Protozoa, with the exception of the amoeba coli, have only rarely 
been found. Kiinstler and Pitres thus observed numerous large 
spores with from ten to twenty crescentic corpuscles in the pus taken 
from the pleural cavity of a man, which closely resembled the 
coccidia of mice. Litten observed cercomonads in the fluid with- 
drawn from a pleural cavity. 

Most important in this connection is the demonstration of the 
presence of the amoeba coli in the pus, and in cases of liver-abscess 
an examination with this view should never be neglected, as the 
prognosis to a large extent will depend upon the results obtained. 
As far as the occurrence of amoebse in pus is concerned, the observa- 
tion of Flexner, who demonstrated their presence in an abscess of 
the lower jaw, goes to show that they should not be looked for in 
the pus of abscesses of the liver only. 

Vermes. Of these, the filaria and hydatids are very rarely ob- 
served in this country. 

Crystals. As has been stated, crystals of cholesterin are frequently 



470 CLINICAL DIAGXOSIS. 

found in old pus and in exudates of long standing, but are rarely 
seen in recent exudates. They may be recognized by their character- 
istic form and their chemical reactions, as described in the chapter 
on Feces (p. 172). Triple phosphates, fatty-acid crystals, and 
ha?matoidin are likewise frequently seen, the presence of the latter, of 
course, indicating a previous admixture of blood. 



CHAPTER IX. 

THE EXAMINATION OF CYSTIC CONTENTS. 

CYSTS OP THE OVARIES AND THEIR APPENDAGES. 

The material obtained from cysts of the ovaries or their append- 
ages varies greatly in character. On the one hand, it may be fluid, 
clear, and of low specific gravity, containing at the same time but 
little albumin, while, on the other, it may be dense, viscous, of colloid 
appearance, and of a specific gravity varying between 1.018 and 
1.024, owing to the presence of a large amount of albumin, viz., 
serum-albumin, serum-globulin, and, most important of all, metal- 
bumin or paralbumin. The latter is almost constantly met with in 
ovarian cysts, and its presence is quite characteristic of fluids derived 
from this source. 

Test for metalbumin. The fluid is mixed with three times its 
own volume of alcohol and set aside for twenty-four hours, when it 
is filtered and the precipitate suspended in water. This is again 
filtered and the filtrate tested in the following manner : 1. A few 
c.c. are boiled, when in the presence of metalbumin the liquid will 
become cloudy, without, however, the formation of a precipitate. 
2. With acetic acid no precipitate is obtained. 3. Upon the appli- 
cation of the acetic acid and potassium ferrocyanide test the liquid 
becomes thick and assumes a yellowish color. 4. When boiled with 
Millon's reagent a few c.c. of the filtrate will yield a bluish-red color, 
while the addition of concentrated sulphuric acid, without boiling, 
gives rise to a violet color. 

The color of cystic fluids may vary from a light straw to a reddish- 
brown, or even chocolate ; the latter color may be observed when 
hemorrhage has taken place into the cyst. 

Of morphologic elements, ovarian cysts contain red blood-cor- 
puscles, leucocytes, and at times fatty granules in large numbers, 
crystals of cholesterin, hsematoidin, and fatty acids. Most important, 
however, from a diagnostic standpoint is the presence of cylindrical 
or prismatic ciliated epithelial cells, derived from the internal lining 



472 



CLINICAL DIAGNOSIS. 



of the cyst, in the presence of which the diagnosis may be definitely 
made. (Fig. 124.) At times such cells cannot be demonstrated, 
owing to their having undergone fatty degeneration ; moreover, if 
the epithelium lining the cyst be squamous in character, it may be 
difficult, if not impossible, to arrive at a satisfactory conclusion from 
an examination of the morphologic elements alone. Colloid con- 
cretions, which may vary in size from several micromillimeters to 
0.1 mm., are occasionally observed, more particularly in eases of 



Fig. 124. 




Contents of an ovarian cyst. (Eye-piece III., obj. 8 a, Reichert.) (v. Jaksch.) 
a. Squamous epithelial cells, b. Ciliated epithelial cells, c. Columnar epithelial cells, d. 
Various forms of epithelial cells, e. Fatty squamous epithelial cells. /. Colloid bodies, g. 
Cholesterin crystals. 

colloid cysts. They may be recognized by their irregular form, 
their homogeneous appearance, their slightly yellowish color, and 
their delicate outlines. 

In dermoid cysts, epidermal cells and occasionally hair are ob- 
served, in which case the diagnosis is no longer doubtful. 

HYDATID CYSTS. 



Hydatid cysts are scarcely ever seen in this country, and may prac- 
tically be excluded in a differential diagnosis. The fluid in question 
is clear, alkaline, of a specific gravity varying between 1.006 and 
1.010, and contains no albumin. Succinic acid is usually present 



THE EX. 1 MIS. 1 TION OF CYSTIC CONTENTS. 473 

and may be demonstrated by acidifying a small amount of the fluid 
with hydrochloric acid and evaporating to dryness. The residue is 
extracted with ether, and the ether evaporated, when the aqueous 
solution of the second residue in the presence of succinic acid will 
yield a rust-colored, gelatinous precipitate when treated with a few 
drops of a solution of the sesquichloride of iron. Sodium chloride 
is always present in notable amounts and may be recognized by 
evaporating a drop of the liquid upon a slide, when the characteristic 
crystals of salt will be found. Most important, of course, is the 
microscopic examination, which may reveal the presence of booklets 
and shreds of membrane, and at times of scolices (see Sputum). 

HYDRONEPHROSIS. 

The diagnosis of hydronephrosis can usually be made without 
difficulty if a sufficient amount of fluid can be obtained, as the pres- 
ence of urea and uric acid in notable quantities, as well as of renal 
epithelial cells, which latter especially should be sought for, is quite 
characteristic. Small amounts of uric acid may also be present in 
ovarian cysts. 

PANCREATIC CYSTS. 

These cysts may be definitely recognized by the fact that the fluid 
possesses the power of digesting albumin in alkaline solutions. A 
small amount of the liquid is added to milk, when after precipitation 
of the casein the biuret test is applied, a positive reaction indicating 
the presence of trypsin. Unfortunately, however, this test does not 
always yield positive results, even if the fluid in question be due 
to a pancreatic cyst, as the trypsin is apparently destroyed in the 
course of time. The larger the size of the cyst, the less likely 
will it be possible to obtain the reaction described. A positive re- 
sult will hence only be of value, while a negative result does not 
exclude the existence of the disease. 



CHAPTER X. 

THE EXAMINATION OF MENINGEAL FLUID. 

Of late, puncture of the meninges has been repeatedly resorted to 
for diagnostic purposes. In cases of tubercular meningitis, tubercle- 
bacilli, contained in the fine flakes which form at the bottom of the 
vessel, may at times be found. More frequently, however, it is 
necessary to resort to inoculation of guinea-pigs with the fluid 
withdrawn. As a rule, the fluid is perfectly clear, with a specific 
gravity of 1.006 or 1.007, and containing but 0.5 to 1 per cent, of 
albumin. A larger amount of the latter usually indicates a more 
intense inflammatory process. In cases of purulent meningitis the 
fluid is more or less cloudy, owing to the presence of large numbers 
of leucocytes. It has been stated that sugar is usually found in 
cases of brain-tumor, while this is but rarely observed -in tubercular 
meningitis. 



CHAPTER XI. 

THE SEMEN. 

DEFINITION. 

The ejaculated semen is a mixture of the secretions furnished by 
the testicles, the prostate gland, the seminal vesicles, and the glands 
of Cowper. 

GENERAL CHARACTERISTICS. 

Semen is white or slightly yellowish in color, semi-fluid, sticky, 
and of a somewhat opaque, non-homogeneous, milky appearance. 
The latter is caused by the presence of white, opaque islets floating 
in the otherwise clear fluid, which consist almost entirely of the 
specific morphologic elements of the semen, the spermatozoa. Its 
odor, strongly resembling that of fresh glue, is very characteristic, 
and is owing to the presence of spermin. It is generally attributed 
to an admixture of prostatic fluid, as the semen obtained from the vasa 
deferentia is odorless. According to Robin, however, this odor is 
only produced at the moment of ejaculation, and cannot be ascribed 
to any single one of the secretions present. The reaction of human 
semen is slightly alkaline, and its specific gravity greater than that 
of water, in which it readily sinks to the bottom. 

CHEMISTRY OP SEMEN. 

Curiously enough no accurate analyses of human semen, or of 
mammalian semen have been made, and only the old analyses of 
Vauquelin and Kollicker can be given. 





Man. 


Horse. 


Ox. 


Water . . . ... 


. 90 


81.9 


82.1 


Albuminous material ) 




f 


15.3 


Extractives . . V 
Ethereal extract . J 


. 6 


\ 16.45 






( 


2.2 


Mineral material . 


. 4 


1.61 


2.6 



476 



CLINICAL DIAGNOSIS. 



The mineral matter appears to consist to a large extent of calcium 
phosphate. 

If semen be kept for any length of time, or if it be slowly evapor- 
ated, crystals of spermin will be seen to separate out. These have 
been shown to be chemically identical with the phosphate of ethylen- 
imin, C 2 H 4 (]SrH), and hence with the so-called Charcot-Leyden 
crystals so frequently seen in asthmatic sputa and in the blood of 
leukemic patients. 

MICROSCOPIC EXAMINATION OF THE SEMEN. 

Upon microscopic examination normal semen will be seen to con- 
tain innumerable, actively moving, thread-like bodies, measuring 
from 50 fi to 60// in length, the spermatozoa. These consist of an 
egg-shaped head, when seen from above, 3 fi to 5 ft in length, the 
broader end being directed anteriorly ; a middle piece, 4// to 6// in 
length, with which the head is united by its smaller end ; and the 
posterior piece or tail, into which the middle piece gradually fades 
(Fig. 125). 

Fig. 125. 




Human semen, a. Spermatozoa, b. Cylindrical epithelium, c. Bodies enclosing lecithin 
granules, d. Squamous epithelium from the urethra., d'. Testicle cells, e. \ Amyloid; cor- 
puscles. /. Spermatic crystals, g. Hyaline globules, (v. Jaksch.) 



In addition to the spermatozoa a few hyaline bodies are seen de- 
rived from the seminal vesicles, numerous small pale granules 'of 
an albuminous nature, some testicular and urethral epithelial cells, 
lecithin-corpuscles, and so-called prostatic or amyloid^ corpuscles, 
which at first sight resemble starch-granules in appearance, owing 
to their concentric striations ; a few leucocytes and occasionally a 
few red corpuscles may also be found. 



THE SEMEN. 477 

PATHOLOGY OP THE SEMEN. 

The study of the semen has as yet received but little attention 
from clinicians, and gynecologists frequently hold the woman respon- 
sible for sterility where an examination of the husband's semen would 
— according to Kehrer in 40 per cent. — reveal an absence of sperma- 
tozoa, constituting the condition usually spoken of as azoospermatism. 
This may be temporarily observed followiug venereal excesses, when 
the fluid finally ejaculated is almost entirely of prostatic origin ; it 
is theu of no further significance, but persistent azoospermatism must 
of necessity be associated with sterility. 

Cases have been recorded in which, notwithstanding the presence 
of spermatozoa and otherwise normal sexual conditions in both hus- 
band and wife, sterility nevertheless existed, but iu which it was 
observed that the spermatozoa lost their motile power almost imme- 
diately after ejaculation, while under normal conditions it is a well- 
known fact that following intercourse actively moving spermatozoa 
may be found in the vagina after many hours, days, or even weeks. 

Whenever it is deemed advisable to make an examination of the 
semen, this should be done immediately following ejaculation, or as 
short a time as possible at least be allowed to elapse, and note be 
taken, not only of the presence, but also of the motility of the sper- 
matozoa, a drop of the semen being mixed with a drop of normal 
(0.6 per cent.) saline solution, and at once examined with the micro- 
scope. 

THE RECOGNITION OP SEMEN IN STAINS. 

In medico-legal cases the physician may be called upon to de- 
cide whether or not certain stains on the linen are caused by sper- 
matic fluid, whether or not a rape has been committed, etc. In 
such cases it is frequently only necessary to examine a drop of the 
vaginal fluid in order to arrive at a positive result at once. At 
other times, however, recourse must be had to the following method : 
A fragment of the linen or scrapings from the vulva or vagina are 
placed in a watch-crystal and allowed to soak for at least one hour in 
from 27 to 30 per cent, alcohol, when a bit of the material is teased 
in a solution of eosin in glycerine (1 : 200), and examined. The 
heads of the spermatozoa are thus stained a deep red, while the tails, 
which are often found broken, exhibit a pale rose-tint and can 
readily be distinguished from any vegetable fibres present, which do 



478 CLINICAL D1A GNOSIS. 

not take up the stain at all. A positive statement cau thus be made 
in every case, even after months or years, as the spermatozoa not 
only resist the action of reagents, but also the process of putrefaction, 
probably owing to the great proportiou of miueral matter which 
enters into their composition, and which insures the preservation of 
their form. Instances have been recorded in which it was possible 
to demonstrate the presence of spermatozoa in stains after eighteen 
years. 

The author found that upon the addition of a drop of an 0.5 per 
cent, alcoholic solution of dimethyl-amido-azo-benzol to a drop of 
urine containing spermatozoa, the heads of the latter were stained a 
distinct blue, while neck and tail remained unstained. 



CHAPTER XII. 

VAGINAL DISCHARGES. 

GENERAL DESCRIPTION. 

The. secretion which is normally furnished by the vaginal glands 
is small in amount and just sufficient to keep the mucous membrane 
moist. It is a clear or somewhat milky-looking, semi-liquid material, 
in which numerous epithelial laminae, which have been thrown off 
during the normal process of desquamation, may be observed upon 
microscopic examination. To the presence of the latter the milky 
and at times pultaceous appearance of the secretion is due. Mucous 
corpuscles, a few large mononuclear leucocytes, cellular detritus, and 
innumerable bacteria, among which the staphylococcus pyogenes 
albus, aureus, and citreus, leptothrix, etc., may be mentioned, are 
also encountered. (Fig. 126.) 

Fig. 126. 




Normal vaginal discharge. 



A peculiar microorganism belouging to the class of infusoria, the 
trichomonas vaginalis, is also not infrequently observed, both in 
normal and pathologically altered vaginal secretion. This parasite, 
which measures about 0.015 mm. in length, is of an oblong, round 
or biscuit-like form, provided with from one to three flagella at one 



480 CLINICAL DIAGNOSIS. 

end, by means of which it actively propels itself about, and a 
somewhat stouter, stiff caudal appendage at the other, while later- 
ally an undulating comb of six or seven cilia may be seen. 

It has been stated that the reaction of the vaginal secretion in 
virgins is invariably acid, while an alkaline reaction is the rule in 
the deflorees. 

VAGINAL BLENNORRHEA. 

In physiologic conditions an increased vaginal secretion is ob- 
served during sexual excitement, especially during coitus, just pre- 
ceding and at the beginning of the process of menstruation and during 
pregnancy, when a profuse blennorrhcea is frequently seen, which 
often assumes a virulent character. The secretion under such 
conditions readily becomes purulent. When not depending upon a 
gonorrhceal infection the secretion is thicker than normal, white and 
creamy. At times also the vaginal catarrh observed in pregnancy 
is complicated with mycosis, when white or yellowish -gray patches 
may be seen at the orifice of the vagina ; the latter may, indeed, 
even be filled with particles which consist entirely of fungi. 

MENSTRUATION. 

At the beginning of menstruation, as has been pointed out above, 
an increase in the amount of vaginal secretion is observed, in which 
leucocytes, prismatic epithelial cells coming from the uterus, as well 
as the usual vaginal cells, may be seen upon microscopic examination. 
Later the secretion becomes sanguinous in character, and finally 
only epithelial cells, leucocytes, and granular detritus are encoun- 
tered, the cells usually showing evidence of fatty degeneration. 

THE LOCHIA. 

The lochia during the first day following parturition are red in 
color, the lochia rubra, and emit the characteristic sanguinous odor. 
At this time a microscopic examination will reveal an abundance of 
red corpuscles, some leucocytes, and a variable number of epithelial 
cells, which are almost entirely of vaginal origin. On the second 
and third days the number of red corpuscles diminishes while the 
leucocytes increase in number. Still later the diminution in the red 



VAGINAL DISCHARGES. 481 

and the increase in the white becomes more marked, the discharge 
at the same time assuming a grayish or white color, until about the 
tenth day the red corpuscles have almost entirely disappeared, while 
the leucocytes and epithelial cells are quite abundant. Finally, the 
secretion becomes thicker, mucoid, and milky-white in color, the 
lochia alba, which condition may persist for from three to four weeks 
in nursing-women, and still longer in those who do not nurse, until 
at last the normal secretion is again observed. Numerous bacteria 
are encountered in the lochia, and it is curious to note that among 
these pus-organisms are quite constantly present, without giving 
rise to any symptoms. In cases of pregnancy, when a portion of 
the placenta or membranes has remained behind, the lochia soon 
give off a fetid odor, and assume a dirty brownish color ; the reten- 
tion of blood-clots alone may also produce this result. In such 
cases the lochia are found to be swarming with bacteria of all kinds. 

VULVITIS AND VAGINITIS. 

In cases of vulvitis and vaginitis a great increase is observed in 
the number of cellular elements, both leucocytes and epithelial cells, 
the character of the latter depending, of course, essentially upon the 
portion of the genital tract affected. Red corpuscles are also met 
with at times, their number generally bearing a direct relation to the 
virulence of the inflammatory process. 

The discharge of large amounts of pure pus through the vagina is 
indicative of the perforation of an abscess of the genital organs or 
of neighboring structures into the uterus or the vagina, but is of 
rare occurrence. Much more common is the discharge of fecal matter 
or of urine through this channel, indicating the existence of a vagino- 
rectal or vagino-vesical fistula. 

MEMBRANOUS DYSMENORRHEA. 

While ordinarily, during the process of menstruation shreds of the 
desquamated uterine lining are frequently encountered, it is rare to 
meet with larger pieces or even entire casts of the uterus, the elimina- 
tion of which is usually associated with the symptoms of a severe 
dysmenorrhcea, constituting the condition generally spoken of as 
membranous dysmenorrhcea. 

.si 



482 



CLINICAL DIAGNOSIS. 



CANCER. 

While the diagnosis of a malignant growth of the uterus has prob- 
ably never been based upon a microscopic examination of the vagiual 
discharge, it may be mentioned that such, however, is possible, as 
fragments of an epithelioma of the cervix, for example, may fre- 
quently be detected upou microscopic examination. (Fig. 127.) 



Fig. V. 



oc, 




Vaginal secretion from a case of epithelioma of the cervix uteri. 

GONORRHOEA. 

Very important is the examination of both vaginal and urethral 
discharges in suspected cases for the presence of gonococci, as it is 
practically impossible to diagnose this condition positively in any 
other manner (see chapter on Urine). 

ABORTION. 



In cases of abortion it is often possible to discover in the blood- 
clots which have been expelled chorion villi, presenting their char- 
acteristic capillary networks (Fig. 1-8), aud often manifesting signs 



VAGINAL DISCHARGES. 



483 



of advanced fatty degeneration. Important also from a diagnostic 
point of view is the presence of decidual cells (Fig. 129), which are 



Fig. 128. 




Decidual cells. 



characterized by their large size, their round, polygonal or spindle- 
like form, and their characteristic nuclei and nucleoli. 



CHAPTEE XIII. 

the secketio:n of the mammary glands. 
the secretion op milk in the newly born. 

A secretion from the mammary glands in the male is only ob- 
served in the newly born, with the exception of some very rare cases 
where adult males were known to suckle infants. The fluid in ques- 
tion, which may also be obtained from the female infant, is termed 
" Hexenmilch " (witches' milk) by the Germans. Qualitatively it 
has the same composition as milk, but may manifest considerable 
quantitative variations. 

COLOSTRUM. 



Aside from those curious instances in which a secretion of milk 
has been observed in non-pregnant adult women, mammary activity 
is essentially connected with the physiologic phenomena of preg- 
nancy and parturition. Often as early as the third month a small 
drop of a serous-looking fluid can be obtained from the nipple by pres- 
sure upon the breasts. Immediately after birth a variable amount 
of fluid is secreted, which is watery, semi-opaque, mucilaginous, and 
of a yellowish color. To this secretion, as well as to that observed 
during pregnancy, the term colostrum has been applied. It is dis- 
tinguished from true milk by its physical characteristics, as well as 
the presence of a greater proportion of sugar and salts. The fluid, 
moreover, is coagulated by boiling. An idea may be formed of its 
chemical composition from the appended tables : 





4 weeks before birth. 


17 davs be- 


9 days be- 


24 hours 


2 days 








fore birth. 


fore birth. 


after birth. 












Water . 


945.2 


852.0 


851.7 


858.8 


843.0 


867.9 


Solids . 


54.8 


148.0 


148.3 


141.2 


157.0 


132.1 


Casein . 












21.8 


Albumin 


28.8 


69.0 


74.8 


80.7 






Fat 


7.3 


41.3 


30.2 


23.5 




48 6 


Lactose 


17.3 


39 5 


43.7 


36.4 




61.0 


Salts . 


4.4 


4.4 


4.5 


5.4 


5.1 





THE SECRETIOS OF THE MAMMARY GLANDS. 485 

Upon microscopic examination minute fat-droplets, a few leuco- 
cytes, some epithelial cells, and so-called colostrum-corpuscles are 
found. These latter are highly retractive bodies ol irregular si/.e, the 
interior of which is tilled with fatty granules. (Fig. 130.) 



Fig. 130. 






o 






Colostrum of a woman in sixth month of pregnancy. (Eye-piece III., obj 8 a, Reichert.) 

(v. Jaksch.) 



THE SECRETION OP MILK PROPER IN THE ADULT 

FEMALE. 

The secretion of milk proper usually begins about the third day 
following parturition, and may continue for a variable length of 
time. On the one baud, the amount of milk secreted may be so 
small as to be insufficient for the wants of the child, so that 
lactation may have to cease after several days. On the other hand, 
women are not infrequently observed who nurse children for two 
years or even longer. As a general rule, however, infants are 
nursed until six or seven teeth have appeared, which period will, of 
course, vary with the individual child, corresponding on an average 
to about the eleventh month. 

HUMAN MILK. 

Human milk is of a bluish color, thus differing from the milk of 
cows. Its reaction is alkaline. Its specific gravity may vary be- 
tween 1.026 and 1.035, one between 1.028 and 1.034 being the 
most common. The amount of milk secreted in twenty-four hours 
varies form 500 to 1500 c.c. 

From a microscopic point of view milk may be regarded as a 
fairly homogeneous emulsion of fat, being practically destitute of 
cellular elements. From the following table an idea may be formed 
of the chemical composition of human milk : 



486 CLINICAL DIAGNOSIS. 



Biehl. Gerber Christerm. Pfeiffer. Pfeiffer. ^^n.^ 



Water . . 


876 


8910 


872.4 


892 


Solids . . 


124 


109 


127.6 


1080 


Albumin . 


22.10 


17.90 


19.00 


16.13 


Fat . . 


38.10 


33.00 


43 20 


3228 


Lactose . 


60.90 


53.90 


59.80 


57.94 


Salts . . 


2.90 


4.20 


2.60 


1 65 



890.6 877.9 

109.4 

1724 25.30 

29.15 38.90 

59.92 55.40 

2.09 2.50 



Upon comparing this table with the following, representing an 
analysis of cow's milk, it will be seen that the latter usually contains 
more albumin and less sugar than human milk. Human milk, 
moreover, is relatively deficient in mineral matter and especially in 
CaO andP 2 5 : 

Water 874.2 

Solids 125.8 

Casein 28 8 \ qa-i 

Albumin 5.3 i 

Fat 36.5 

Lactose 48.1 

Salts 7.1 

The albumins which are found in milk-plasma are casein, lacto- 
globulin, and lactalbumin. It is claimed by numerous observers that 
the casein of human milk differs from that obtained from cows' milk. 
There can be no doubt that the casein-coagula in the former case 
are not so large and dense as those observed in cow's milk. Human 
casein, moreover, is not so readily precipitated by means of acids aud 
salts ; it does not always coagulate in the milk upon the addition of 
rennet ferment, and while it can be precipitated by the gastric juice 
it is readily dissolved by an excess. Although accurate analyses of 
human casein do not exist as yet, the view that the two forms are 
not identical appears very probable (Hammarsten). 



THE MILK IN DISEASE. 

The chemistry of the milk in pathologic conditions has received 
but little attention. It appears, however, that the milk of women, 
while ill, usually contains less fat, and that the proportion of lactose 
is diminished. In cases of jaundice the presence of bile-pigment 



THE SECRETION OE THE MAMMARY GLANDS. 



487 



Pig. LSI. 



and of biliary acids lias not as yet been satisfactorily demonstrated. 
In cases of mammary tumors bloody secretion has been observed in 
rare cases, the nipple itself being intact. 

Microscopically an admixture of leucocytes is 
observed in diseases of the breast, and especially in 
cases of abscess. The question whether or not 
normal human milk contains microorganisms may 
now be answered in the affirmative, as recent 
researches have shown that the staphylocccus 
pyogenes albus is almost always present, and 
that the staphylococcus aureus is also at times, 
though rarely, found. The streptococcus is said 
to occur only in cases of infection. The tubercle- 
bacillus, according to v. Jaksch, is also occasion- 
ally present in cases of phthisis, a very important 
observation. A blue and red color has at times 
been observed in the milk of cows, due to the 
presence of the bacillus cyanogenus and the micro- 
coccus prodigiosus. 



THE EXAMINATION OF COW'S MILK. 

Most important is the determination of the 
specific gravity and of the amount of fat. The 
former in a reliable article may vary between 
1.029 and 1.033. The amount of fat should not 
be less thau 3 per cent. 



Determination of the Specific Gravity. 

The specific gravity is best determined with 
the lactodensimeter of Quevenne. (Fig. 131.) 
As the instrument is registered for a tempera- 
ture of 60° F., it is necessary to correct the 
specific gravity whenever the temperature rises Quevenne's lactodensi- 
above or falls below this point. In the following meter< 

tables the corrected specific gravity may be found corresponding to 
temperatures ranging from 46° to 75° F. 




488 



CLINICAL DIAGNOSIS. 



Corrections for Temperature. 



Specific 
gravity. 



Degrees of thermometer (Fahrenheit). 



1020 
1021 
1022 
1023 
1024 
1025 
1026 
1027 
1028 
1029 
1030 
1031 
1032 
1033 
1034 
1035 



46 


47 


48 


49 


50 


51 


19.0 


19.1 


19.1 


19.2 


19.2 


19.3 


20.0 


20.0 


20.1 


20.2 


20.2 


20.3 


21.0 


21.0 


21.1 


21.2 


21.2 


21.3 


22.0 


22.0 


22.1 


22.2 


22.2 


22.3 


22.9 


23.0 


23.1 


23.2 


23.2 


23.3 


23.9 


24.0 


24.0 


24.1 


24.1 


24.2 


24.9 


24.9 


25.0 


25.1 


25.1 


25.2 


25.9 


25.9 


26.0 


26.1 


26.1 


26.2 


26.8 


26.8 


26.9 


27.0 


27.0 


27.1 


27.8 


27.8 


27.9 


28.0 


28.0 


28.1 


28.7 


28.7 


28.8 


28.9 


29.0 


29.1 


29.6 


29.6 


29.7 


29.8 


29.9 


30.0 


30.5 


30.5 


30.6 


30.7 


30.9 


31. 


31.4 


31.4 


31.5 


31.6 


31.8 


31.9 


32.3 


32.3 


32.4 


32.5 


32.7 


32.9 


33.1 


33.2 


33.4 


33.5 


33.6 


33.8 



52 


53 


19.4 


19.4 


20.3 


20.4 


21.3 


21.4 


22.3 


22.4 


23.3 


23.4 


24.3 


24.4 


25.2 


25.3 


26.2 


26.3 


27.2 


27.3 


28.2 


28.3 


29.1 


29.2 


30.1 


30.2 


31.1 


31.2 


32.0 


32.1 


33.0 


33.1 



54 



55 



33.9 



34.0 



19.5 


19.6 


20.5 


20.6 


21.5 


21.6 


22.5 


22.6 


23.5 


23.6 


24.5 


24.6 


25.4 


25.5 


26.4 


26.5 


27.4 


27.5 


28.4 


28.5 


29.4 


29.4 


30.3 


30.4 


31.3 


31.4 


32.3 


32.4 


33.2 


33.3 


34.2 


34.3 



Specific 
gravity. 



1020 
1021 
1022 
1023 
1024 
1025 
1026 
1027 
1028 
1029 
1030 
1031 
1032 
1033 
1034 
1035 



Degrees of thermometer (Fahrenheit). 



56 



19.7 
20.7 
21.7 
22.7 
23.6 
24.6 
25.6 
26.6 
27.6 
28.6 
29.6 
30.5 
31.5 
32.5 
33.5 
34.5 



57 



19.8 
20.8 
21.8 
22.8 
23.7 
24.7 



34.6 



19.9 
20.9 
21.9 
22.8 
23.8 
24.8 
25.8 
26.8 
27.8 
2*. 8 
29.8 
30.8 
31.7 
32.7 
33.7 
34.7 



59 


60 


19.9 


20.0 


20.9 


21.0 


21.9 


22.0 


22.9 


23.0 


23.9 


24.0 


24.9 


25.0 


25.9 


26.0 


26.9 


27.0 


27.9 


28.0 


28.9 


29.0 


29.9 


30.0 


30.9 


31.0 


31.9 


32.0 


32.9 


33.0 


33.9 


34.0 


34.9 


35.0 



61 



20.1 
21.1 
22.1 
23.1 
24.1 
25.1 
26.1 
27.1 
28.1 
29.1 
30.1 
31.2 
32.2 
33. 2 
34.2 
35.2 



62 


63 


20.2 


20.2 


21.2 


21.3 


22.2 


22.3 


23.2 


23.3 


24.2 


24.3 


25.2 


25.3 


26.2 


26.3 


27.3 


27.4 


28.3 


28.4 


29.3 


29.4 


30.3 


30.4 


31.3 


31.4 


32.3 


32.5 


33.3 


33.5 


34.3 


34.5 


35.3 


35.5 



64 


65 


20.3 


20.4 


21.4 


21.5 


22.4 


22.5 


23.4 


23.5 


24.4 


24.5 


25.4 


25.5 


26.5 


26.6 


27.5 


27.6 


28.5 


28.6 


29.5 


29.6 


30.5 


30.7 


31.5 


31.7 


32.6 


32.7 


33.6 


33.8 


34.6 


34.8 


35.6 


35.8 



Specific 
gravity. 



Degrees of thermometer (Fahrenheit). 



1020 
1021 
1022 
1023 
1024 
1025 
1026 
1027 
1028 
1029 
1030 
1031 
1032 
1033 
1034 
1035 



20.5 
21.6 
22.6 
23.6 
24.6 
25.6 
26.7 
27.7 
28.7 
29.8 
30.8 
31.8 
32.9 
33.9 
34.9 
35.9 



20.6 
21.7 
22.7 
23.7 
24.7 
25.7 
26.8 
27.8 
28.8 
29.9 
30.9 
32.0 
33.0 
34.0 
35.0 
36.1 



20.7 
21.8 
22.8 
23.8 
24.9 
25.9 
27.0 
28.0 
29.0 
30.1 
31.1 
32.2 
33.2 
34.2 
35.2 
36.2 



20.0 
22.0 
23.0 
24.0 
25.0 
26.0 
27.1 
28.1 
29.1 
30.2 
31.2 
32.2 
33.3 
34.3 
35.3 
36.4 



70 


71 


72 


73 


74 


21.0 


21.1 


21.2 


21.3 


21.5 


22.1 


22.2 


22.3 


22.4 


22.5 


23.1 


23.2 


23.3 


23.4 


23.5 


24.1 


24.2 


24.3 


24.4 


24.6 


25.1 


25.2 


25.3 


25.5 


25.6 


26.1 


26.2 


26.4 


26.5 


26.6 


27.2 


27.3 


27.4 


27.5 


27.7 


28.2 


28.3 


28.4 


28.6 


28.7 


29.2 


29.4 


29.5 


29.7 


29.8 


30.3 


30.4 


30.5 


30.7 


30.9 


31.3 


31.5 


31.6 


31.8 


31.9 . 


32.4 


32.5 


32.6 


32.8 


33.0 ! 


33.4 


33.6 


33.7 


33.9 


34.0 


34.5 


34.6 


34.7 


34.9 


35.1 i 


35.5 


35.6 


35.8 


36.0 


36.1 


36. 5 


36.7 


36.8 


37.0 


37.2 

1 



75 



21.6 
22.6 
23.7 
24.7 
25.7 
26.8 
27.8 
28.9 
29.9 
31.0 
32.1 
33.1 
34.2 
35.2 



37. 



THE SECRETWX OF TEE MAMMARY GLANDS. 



489 



The Estimation of Pat. 

The estimation of the fat is most conveniently made by means of 
the lactoscope of Feser, pictured in Fig 132. Milk is drawn into 
the pipette up to the mark M, when it is emptied into the cylinder 
C. The former is then at once rinsed with water and the wash- 
ings added to the milk. While shaking, water is further added, 



Fig. 132. 



'« 80- 




Feser's lactoscope. 



until the black lines upon the milk-colored glass plug A can 
just be discerned. The figure upon the right of the scale which is 
reached by the mixture will then directly indicate the percentage- 
amount of fat, while the number upon the left indicates the amount 
of water that has been added. 



INDEX. 



ABORTION, vaginal discharge in, 482 
Abscess of the liver with perfora- 
tion into the lung, 235 
Abscess, pulmonary, 235 
Absorption, rate of, in the stomach, 156 
Acetic acid, 143 

tests for, 144 
Acetone in the blood, 48 

in the gastric contents, 147 

in the urine, 407 

tests for, 408 
Acetonemia, 48 
Acetonuria, 407 
Acetvlene-poisoning, blood-changes in, 

3o 
Acholic stools, 180 
Acid, acetic, 143, 144, 171 

0-oxybutyric, 409 

benzoic, 325 

butyric, 143, 144, 171 

capric, 170 

caproic, 170 

carbolic, 2S1 , 399 
tests for, 406 

diacetic, 407, 408, 409 

diazo-benzene-sulphonic, 403 

formic, 171 

hippuric, 322 

homogentisinic, 400 

hydrochloric, 112 

isobutyric, 170 

laclic/410 

nitric, 354 

oleic, 170 

oxalic, 331 

palmitic, 170 

phosphoric, 270 

picric, 360, 361 

propionic, 170 

salicylic, 399 

succinic, 472 

sulphanilic, 403 

sulphuric, 280 

uric, 311 

uroleucic, 400 

valerianic, 171 
Acidity of the urine, determination of, 

257 
Acids, organic, in the gastric contents, 
144 



Actinomyces hominis, 230 
Actinomycosis, 230 
Acute yellow atrophy, urine in, 289 
Albumin, amount of, 348 
in the feces, 201 
in the gastric contents, 133 
in the urine, 335 
tests for, 253 
boiling, 357 
nitric acid, 354 
picric acid, 360 
potassium ferrocyanide, 358 
Spiegler's, 360 
trichloracetic acid, 359 
special test for serum-albumin, 363 

for serum-globulin, 363 
quantitative estimation of, 360 
Albuminimeter, Esbach's, 361 
Albuminuria, 335 
accidental, 347 
colliquative, 342 
cyclic, 337 
Da Costa's. 336, 339 
digestive, 346 
febrile, 340 
functional, 337, 339 
hematogenous, 339, 344 
in organic diseases of the kidneys, 

339 
intermittent, 337 
mixed, 347 
neurotic, 345 
physiologic, 335 
postural, 337 

referable to circulatory disturbances, 
343 
to impeded outflow of urine, 244 
toxic. 345 
transitory, 337 
Albumoses in the blood, 41 

in the gastric contents, 129 
in the urine, 348 
tests for, 133, 364 
Albumosuria, 348 
Alkaline stools, 166, 175 

urine, 256 
Alkalinity of the blood. 20 

estimation of, 21 
Alkapton in the urine, 399 
Alkaptonuria, 399 



492 



INDEX. 



Almen's solution, 373 

Alveolar epithelium, 222 

Amido-acids, 288 

Ammonia in the gastric contents, 146 

Ammoniacal fermentation, 255 

Ammonio-magnesium phosphate, 420 

Ammonium urate, 430 

Amoeba coli, 183, 214, 225, 469 

Amcebas in the urine, 459 

Amoebic colitis, 182 

Amorphous hsematoidin, 38, 232, 428 

Amphoteric urine, 254 

Amyloid corpuscles in the semen, 476 

Anachlorhydry , 1 1 

Anacidity, hysterical, 111 

Anaemia, albuminuria in, 344 

blood in, 28 

pernicious, blood-changes in, 50, 85 

simple secondary, 85 
Anchylostoma duodenale, 194 
Anchylostomiasis, 181,194 
Anguillula intestinalis, 195 

stercoralis, 196 
Anguilluliasis, 182 
Aniline dyes, classification of, 57 

water, gentian-violet, 228 
Animal gum in the urine, 383 
Animal parasites in the blood, 77 
in the feces, 182 
in the sputum, 224 
Annelides, 192 
Anthomyia, 183 
Anthracosis of the lung, 238 
Anthrax, bacillus of, 76 
Anuria. 247 

Aromatic oxy-acids, 400 
Ascarides in the feces, 192 

in the urine, 459 
Ascaris lumbricoides, 182, 192 

mystax, 193 
Asiatic cholera, bacillus of, 197 

feces in, 208 
Asthma, bronchial, Charcot-Leyden 

crystals in, 210, 235 
Atrophy, gastric, 159 
Aurantia, 62 
Azoospermatism, 477 



BACILLI of Booker, 200 
Bacillus coli communis, 200 
in exudates, 466 
in the urine, 458 
Bacillus of anthrax, in the blood, 76 
in the mouth, 108 
of cholera Asiatica, 197 
of diphtheria, 91 
of Finkler and Prior, 177 
of glanders, in the blood, 73 

in the nasal discharge, 210 
of influenza, in the blood, 74 
in the sputum, 230 
lactis aerogenes, 200 



Bacilli of Le Sage, 200 
of smegma, 457 

of tuberculosis, methods of staining, 
227 
in the blood, 73 
in the feces, 200 
in the meningeal fluid, 474 
in the mouth, 108 
in the nasal discharge, 210 
in the sputum, 225 
in the urine, 456 
of typhoid fever, in the blood, 74 
in the feces, 198 
Bacteria in the blood, 72 
in exudates, 469 
in the feces, 197, 165 
in the gastric contents, 153 
in the milk, 487 
in the mouth, 88 
in the nasal secretion, 210 
. in the sputum, 225 
in the urine, 456, 458 
in the vagina, 479 
Bacterial decomposition of the urine, 255 
Bacteriuria. 456 
idiopathic, 458 
non-pathogenic, 458 
Balantidium coli, 186 
Barfoed's reagent, 134 
Basic aniline dyes, 57 

phosphate of magnesium, 421 
i Basophilic leucocytes, in the blood, 59 

in the sputum, 235 
Benzoic acid in the urine, 325 
Benzo-purpurin test for hydrochloric 

acid, 115 
Bile-pigment, in the blood, 47 
in the feces, 202 
in the gastric contents, 150 
in the urine, 393 
tests for, 395 

Gmelin's, 396 
Huppert's, 395 
Rosenbach's, 396 
Rosin's, 395 
Smith's, 395 
Bilharzia hsematobia, 84 
Biliary acids in the blood, 47 
in the feces, 173 
in the urine, 396 
tests for, 173 ♦ 
Bilirubin, 394 
Bismarck-brown, 228 
Biuret test, 296 
Blood, 17 

acetone in, 48 
albumin in, 23 
alkalinity of, 20 
bacteriology of, 72 
biliary constituents of, 47 
carbohydrates in, 41 
cellulose in, 33 
coagulation of, 23 



INDEX. 



493 



Blood, color of, 17 

fat in, 45 

fatty acids in, 45 

fibrin in, 23 

gases in, 26 

general characteristics of, 17 
chemistry of, 23 

glycogen in, 42 

lactic acid in, 46 

odor of, 18 

organic acids in, 44 

parasites in, 72 

parasitology of, 72 

peptone in, 41 

pigments of, 26 

proteids in, 40 

protozoa in, 77 

reaction of, 20 

specific gravity of, 18 

tests for, H66 

gnaiacnm, 366 
Heller's, 366 

urea in 43 

uric acid in, 44 

in anaemia, 85 

in chlorosis, 28, 85 

in the feces, 176, 181 

in the gastric contents, 150 

in the sputum, 214, 221 

in the urine, 351, 440 

-corpuscles, red, 17, 24 

enumeration of, 65, 72 
nucleated forms of, 50 
variations in form of, 49 
in number of, 49 
in size of, 48 

-corpuscles, white (see Leucocytes ,51 

drying and staining of, 60 

medico-legal test for, 37 

-plasma, 17, 24 

-plates, 64 

-serum, 23, 24 

-shadows, 440, 442 
Boas's bulbed stomach-tube, 99 
Bodo urinarius, 459 
Bothriocephalus latus, 190 
Bottger's test for sugar, 373 
Bronchial asthma, 210, 235 
Bronchitis, acute, 234 

chronic, 234 

fibrinous, 235 

putrid, 234 
Browning's spectroscope, 40 
Buccal secretion (see Saliva), 86 
Butyric acid, in the gastric contents, 143 
test for, 144 



c 



ADAVERIX, 423 

Calcium carbonate, crystals of, 431 
phosphate, crystals of, 421 
sulphate, crystals of, 423 



Calliphora erythrocephala, 183 

Calomel stools, 111 I 
Cancer of the stomach, 154 
Carbohydrates, digestion of, 131 

in the blood, 41 
in the feces, 202 
in the urine, 366 
tests for, 134 
Carbol-fuchsin, 228 
acid, estim; 
tests for, 406 
Carbolo-chloride of iron, test for lactic 

acid, 138 
Carbonic oxide, detection of, 147, 374 

haemoglobin, 35 
Caries of the teeth, 86 
Casein, digestion of, 130 

in the milk, 486 
Casts urinary, 443 

classification of, 443 
examination of, 443 
fatty, 447 
granular, 444 
hyaline, 444 
staining of, 444 
waxy, 447 
Catarrh, acute intestinal, 205 
bronchial, 234 
chronic intestinal, 206 
duodenal, 206 
intestinal, of infants, 207 
of ileum, 206 
of jejunum, 206 
of large intestine, 206 
Catheterization of the ureters, 442 
Cellulose in the blood, 43 
Cercomonas intestinalis, 186 
Cerebro-spinal fluid, 210, 474 
Cestodes, 182 
Chalicosis, 231 

Charcot Levden crystals, in the feces, 
163, 181 
in the nasal discharges, 210 
in the sputum, 220, 231 
Chemical examination of the blood, 23 
of the buccal secretion, 86 
of cystic fluids, 471 
of the feces, 166, 201 
of the gastric juice, 101 
of the milk, 487 
of the pus, 467 
of the semen, 475 
of the sputum, 233 
of transudates. 463 
of the urine, 258 
Chlorides in the urine, 260 
estimation of, 263 

according to Neubauer and 

Salkowski, 269 
according to Salkowski and 

Volhard, 263 
direct method, 268 



494 



INDEX. 



Chlorides in the urine, test for, 263 
Chloride of zinc solution, 328 
Chlorosis, blood-changes in, 85 
Cholsemia, 47 

Cholera, Asiatica, 197, 208 
bacillus of, 197 
infantum, 200 

nostras, 198, 207 
-red, reaction of Brieger, 198 
Choluria, 394 
Cholesterin in the blood, 25 

in the feces, 171 

in the sputum, 232 

in the urine, 396 

test for. 172 
Chorion villi, 453 
Chromogens in the urine, 384 
Chyluria, 84, 352, 410 
Chymosin, 126 

estimation of, 128 

test for, 128 
Chyniosinogen, 126 

estimation of, 128 

test for, 128 
Ciliated epithelium, in cysts, 471 

in the sputum, 222 
Cladothrix, 230 
Clostridium-butyricum, 165 
Coating of the tongue, 91 
Coccidia in the feces, 186 
Coffin-lid crystals, 420 
Colica mucosa, 178 

Colloid concretions in ovarian cysts, 472 
Colostrum, 484 

corpuscles, 485 
Comma bacillus. 197 
Concretions biliary, 178 

fecal, 178 

intestinal, 179 

pulmonary, 220 
Congo-red, test for, 111 
Conjugate sulphates, 405 
Constipation, 174, 204 
Contracted kidney (see Nephritis 

atrophica) 
Copaiba-balsam, 357 
Corpora amylacea, 476 
Cow's milk, examination of, 487 
Cresol in the feces, 170 

in the urine, 405 
Crystals of calcium carbonate, 431 
phosphate, 421, 430^ 
sulphate, 423 

of Charcot-Levden, 163, 181, 210, 
220, 231 

of cholesterin, 25, 171, 17^, 232, 396 

of cystin, 423 

of fattv acids, 428 

of htematoidin, 38, 232, 428 

of hsemin, 36 

of hippuric acid, 422 

of indigo, 389, 411 



Crystals of leucin, 424 

of magnesium phosphate, 421 

of oxalate of calcium, 418 

of phenylglucosazon, 375 

of phosphate of spermin, 476 

of Teichmann, 36 

of triple phosphate, 420, 431 

of tyrosin, 424 

of urate of ammonium, 430 

of uric acid, 416 

of xanthin. 427 
Curschmann's spirals. 218 
Cylinders, mucous, 444 

urinarv, 443 
Cylindroids, 413, 449 
Cylindruria, 443 

sine albuminuria, 450 
Cvsticercus cellulose, 189 
Cystin, 423 
Cystinuria, 423 
Cysts, colloid, 472 

contents of, 471 

dermoid, 472 

hydatid, 472 

ovarian, 471 

pancreatic, 473 



D ALAND'S hamatokrit, 70 
Decidual cells, 453 
Denaturization, 129 
Dermoid cysts, 459, 472 
Deutero-albumose, 129 
Dextrin in the urine, 383 
Dextrose in the urine. (See Glucose.) 
Diabetes, 369 

elimination of sugar in, 369 
of urea in, 293 

alternans, 314 

hepatogenic, 371 

Hirschfeld's form of, 294, 295, 375 

insipidus, 246, 263 

myogenic 371 
Diacetic acid in the urine, 407, 408 

test for, 409 
Diaceturia, 408 
Diamines in the urine, 423 
Diarrhoea, 174, 202 
Diathesis, uric acid, 313 
Diazo-reaction (see Ehrlich's reaction), 

401 
Differential table of the more important 

diseases of the blood, 85 
Digestion, gastric, 128 

of albumins, 132 

of albuminoids, 130 

of carbohvdrates, 130 

of milk, 130 

of native albumins, 128 

products of, 128 
Dilatation of the stomach, 159 
Dimethyl-amido-azo-benzol, 112 






INDEX. 



495 



Diphtheria, 91 
Diplococcus pneumonia?, 229 
Distoma haematobium, S4 

hepaticum, 190 

lanceolatum, 192 

pulmonale, 225 

rhatonisi, 192 

urinse, 459 
Donne's pus-test, 487 
Drop-culture of the cholera bacillus, 197 
Drosophila melanogastra, 183 
Drugs, effect of, on the color of the 

stools, 161 
Dysentery, 207 

amoebic, 207 

tropical, 184 
Dyspepsia, secondary, 107 



EARTHY phosphates, 420, 431 
Echincocci, 220, 224, 459 
Ehrlich's granulations, 57 
reaction, 401 
staining methods, 60 
Elastic tissue in the sputum, 216, 223 
Emerald-green test for hydrochloric acid, 

114 
Enteritis, acute, 205 
chronic, 206 
membranosa, 178, 207 
mucosa (see Membranosa), 207 
Enterogenic peptonuria, 349 
Enteroliths, 179 
Eosinophilic leucocytes, in the blood, 59 

in the sputum, 235 
Eosin, staining with, 62 
Epithelial cells, alveolar, 222 
ciliated, 222 

in the buccal secretion, 88 
in the feces, 163 
in the sputum, 221 
in the urine, 432 
in the vaginal secretions, 479 
Erythrodextrin, test for, 134 
Esbach's albuminimeter, 361 

method of estimating albumin, 361 
reagent, 360 
Euchlorhydry, 110 
Ewald's modification of Mohr's test for 

hydrochloric acid, 114 
Extractives in the blood, 25 
Exudates, 461 

albumin in, 462 

in cancer, 465 

chylous appearance of, 465 

coagulation of, 463 

hemorrhagic, 465 

purulent, 466. (See Pus.) 

putrid, 466 

serous, 464 

specific gravity of, 462 

in tuberculosis, 465 



FAT in the blood, 25, 45 
in the milk, estimation of, 489 
Fattv acids in the blood, 45 

clinical significance of, 142 
estimation of, 144 
in the feces, 165, 170 
in the gastric contents, 142 
in the pus, 470 
in the sputum 232 
in the urine, 410 
mode of formation of, 142 
tests for, 170 
Fatty casts, 447 
Febrile acetonuria, 407 
albuminuria, 340 
urobilin, 397 
Fecal matter in the urine, 459 

vomiting, 151 
Feces, 160 

alimentary detritus in, 161 
amount of, 160, 175 
blood in, 176, 181 
chemistry of, 166, 201 
color of, 161, 175 
composition of, 166 
consistence of, 161, 175 
crystals in, 163, 181 
examination of normal feces, 160 
foreign bodies in, 162 
gases in, 166 

general characteristics of, 160 
insects in, 183 

macroscopic constituents of, 161 
microscopic constituents of, 162, 180 
number of stools, 160, 174 
odor of, 161, 175 
parasites in, 164 
pathology of, 174 
reaction of, 166, 175 
worms in, 164 
Fehling's solution, 373 
test for sugar, 372 
Ferment, milk-curdling, 126 

of saliva, 87 
Fermentation test for sugar, 374 
Ferments in the gastric juice, 123 

in the urine, 411 
Feser's lactoscope, 489 
Fibrin, 23 

estimation of, 41 
ferment, 24 
in the blood, 24 
in the urine, 351 
test for, 366 
Fibrinogen, 23 
Fibrinoglobulin, 23 
Fibrinous casts, 217 

coagula in the sputum, 217 

in the urine (see Chyluria), 84, 
352,410 
Filaria sanguinis hominis, 83, 411, 459 
Finkler-Prior bacillus, 177 



496 



INDEX. 



Forceps, cover-glass, 60 

Foreign bodies in the feces, 162 
in the sputum, 220 
in the urine, 459 

Formic acid, detection of, 171 

Franker s pneumococcus, 229 

Fuchsin solution, 228 

Furfurol test for bile acids, 47 



GABBETT'S staining method, 228 
Gall-stones in the feces, 178 
analysis of, 179 
Gangrene of the lung, 234 
Garrod's test for uric acid in the blood, 

54 
Gases in the blood, 26 

in the gastric contents, 145 
in the urine, 411 
Gastric contents, examination of, 94. 
(See also Gastric juice. ) 
juice, 94 

acetic acid in, 148 
acidity of, 102 
amount of, 100 
antiseptic properties of, 108 
aspiration of 99 
butyric acid in, 143 
cause of acidity of, 102 
chemical composition of, 101 

examination of, 101 
expression of, 98 
ferments in, 123 
gases in, 145 

general characteristics of, 100 
hyperacidity of. Ill 
hypersecretion of, 101 
indirect examination of, 157, 

158 
lactic acid in, 134 
method of determining the total 

acidity of, 104 
method of obtaining, 98 
milk-curdling ferment of, 126 
organic acids in, 142 
pepsin in, 123 
proteids in, 128 
secretion of, 94 
zymogens in, 123 
ulcer, 159 
Gastritis, acute, 159 
atrophic, 159 
chronic, 159 
Gigantoblasts (see Megaloblasts), 50 
Glanders, bacillus of, 73 
Glucose, 367 

Bottger's test for, 373 

differential density-method of 
estimating, in the urine, 379 
Einhorn's method, 380 
Fehling's method, 377 
test for, 373 



Glucose, Fermentation test, 374 

Method of Cause, 379 

Xy landers test, 373 

Phenyl-hydrazin test, 375 

Polarimetric method, 376, 381 

Quantitative estimation of, 377 

Tests for. 372 

Trommer's test for, 372 
Glycogen, in the blood, 42 

in the sputum, 233 

test for, 42 
Glycosuria, 367 

alimentaire, 367 

persistent, 369 

transitory, 368 
Glycosuric acid, 374, 400 
Gmelin's reaction, 202 
Gonococcus of Xeisser, 457 

staining of. 458 
Gonorrhoea in the female, 482 

in the male, 439 
Gonorrheal threads in the urine, 439 
Gout, blood in, 44 

urine in, 313 
Gowers' haemoglobinometer, 32 
Gram's method of staining, 92 
Grape sugar. iSee Glucose.) 
Guaiacum test for blood, 366 
Gunzburg's packages, 89, 157 

reagent, 157 
Gum, animal, 383 



H^MATEMESIS, 151 
Haematin, 35, 392 
Haeniatinuria, 350 
Haematoidin. in the blood, 38 

in the sputum, 232 

in the urine, 428 
Haematokrit, 69, 416 
Haematoporphyrin, in the blood, 38 

in the urine, 393 
Heematoxvlin solution, 466 
Hgematuria, 351. 440, 441, 442 
Haemin (see Teichmann's crystals), 36 
Haemoeytometer of Thoma Zeiss, 65 
Haemoglobin, 17. 26 

carbon dioxide, 35 

carbon monoxide, 34 

estimation of, with Fleischl's haemo- 
meter, 29 

estimation of with Gowers' haemo- 
globinometer, 32 

nitric oxide, 34 

sulphuretted hydrogen, 85 

tests for, 365 

in the urine, 350 
Haemaglobinaemia, 33, 350 
Haemoglobinometer of Gowers', 32 
Haemoglobinuria, 33, 350 
Haemometer of Fleischl, 29 
Haemophilia, 24 



INDEX. 



497 



Haycraft's mot hod of estimating uric 

acid, -">17 
Hay em's fluid, (56 
Heart disease, cells of, 237 

sputum in. 237 
Heller's test, for albumin, 355 

for blood, 366 
Hepatogenic icterus, 394 
Hippuric acid in the urine, 322 
estimation of, 325 
properties of, 324 
test for, 325 
Histon in the urine, 353 

test for, 353 
Hoffmann's test for tyrosin, 427 
Hofmeister's test for leucin, 427 
Homogentisinic acid, 400 
Honialomyia, 183 
Hiifner's apparatus for the estimation of 

urea, 306 
Huppert's test for bile-pigment, 395 
Hydatid cysts 472 

echinococcus membrane and 

hooklets in, 473 
sodium chloride in, 473 
succinic acid in, 472 
Hydrochloric acid in the gastric juice, 
107 
amount of, 110 
combined, 115 
free, 108 

quantitative estimation 
of, 117 
according to Leo. 122 

to Martius and Liittke, 119 
to Topfer, 117 
significance of, 108 
source of, 107 
tests for, 112 
Hydrobilirubin, 174 
Hydrocele fluid, 464 

cholesterin in, 464 
Hydrochinon in the urine, 399 
Hydrocyanic acid poisoning, blood- 
changes in, 35 
Hydronephrosis, 473 
Hydrothionuria, 411 
Hypalbuminosis, 40 
Hyperalbuminosis, 40 
Hyperchlorhydry, 111 
Hyperinosis, 40 
Hyperisotonia, 25 
Hyperleucocytosis, 53 
pathologic, 55 
physiologic, 53 
Hypersecretio acida et continua, 106, 

111 
Hypersecretion, 101 
Hypinosis, 41 
Hypochlorhydry, 110 
Hypoleucocytosis, 53 
Hypoxanthin in the urine, 331 



ICTERUS, 394 
1 hematogenic, 89 1 
hepatogenic, 3"4 

neonatorum, 39 I 

urobilin, 397 
Idiopathic bactcriuria, L58 

oxaluria, 333 
Indican in the urine, 386, 389 

test for, 153 
[ndicanuria, 158, 386 
Indigo blue in the urine. 389, 411, 447 

-red in the urine, 390 
Indigosuria, 389, 411 
Indol in the feces, 168 
Indoxyl. 281 

sulphate (see Indican). 
Influenza, bacillus of, 74 
Infusoria in the feces, 186 

in the pus, 469 

in the vaginal discharge, 479 
Inosit in the urine, 384 
Insects in the feces, 197 
Intermittent albuminuria, 337 
Intestinal catarrh, 205 

putrefaction, 158, 168, 386 

tuberculosis, 200 
Intestines, diseases of, 205 
Iodine in the urine, test for, 390 
Iodoform-test for lactic acid, 139 
Iodo-potassium iodide test for micro- 
organisms, 165 
Isotonia, 25 

TAFFE'S test for indican, 539 
J Jaundice (see Icterus), 394 

KIDNEY, amyloid, 447, 448, 460 
atrophic, 460 

large white, 460 
Kreatin, 326 

properties of, 327 
Kreatinin, 326 

estimation of, 329 

properties of, 327 

test for, 328 

-zinc chloride, 328 
Kronig's sputum plate, 218 

T ACTIC acid, bacillus of, 134 
Jj fermentation, 135 

in the blood, 46 
in the gastric contents, 184 

clinical significance of, 

134 
estimation of, 140 
mode of formation, 134 
tests for, 127 
Boas'. 140 
Kelling's, 138 
Strauss', 138 
Uffelmann's, 137 



?y> 



498 



INDEX. 



Lactic acid in the urine, 410 

Lactodensirneter of Quevenne, 487 

Lactoscope of Feser. 489 

Lactose in the urine, 383 

Laiose in the urine, 383 

Landois' estimation of the alkalinity of 

the blood, 21 
Latent microbism, 73 
Laveran's organism, 77, 185 
Laverania malaria;, 81 
Lecithin in the blood, 25 
Legal's test for acetone, 408 
Leo's method of estimating hydrochloric 

acid, 122 
Leprosy, bacillus of, 227 
Leptothrix buccalis, 91 

pulmonalis. 235 
Leucin 232, 293 
Leucocytes, basophilic, 59 

differential enumeration of, 64, 69 

differentiation according to their 
behavior toward aniline dyes, 
57 

Ehrlich's granulations in, 59 

eosinophilic, 58 

estimation of the number of, 64, 67, 
69 

general differentiation of the various 
forms of. 56 

in the blood, 51 

in the exudates, 464 

in the feces, 163. 181 

in the sputum, 220 

in the urine, 435 

lymphocytes, 58 

Mastzellen, 59 

myelocytes, 59 

neutrophilic, 58 

variations in number of, 52 
Leucocytosis, 53 

digestive form of, 53 
Leukaemia, blood in, 18, 85 
Levulose in the urine, 383 
Lieben's test for acetone, 408 
Lipacidaemia, 45 
Lipaciduria, 410 
Lipsemia, 45 
Lipuria, 410 
Liver abscess, 184, 235 

acute yellow atrophy of, 289 

diseases of, feces in (see Acholic 
stools), urine in (see Bile-pig- 
ments). 
Lochia, 4.^0 

alba, 481 

rubra, 480 
Loffler's bacillus, 91 

methylene-blue solution, 92 
Ludwig-Salkowski's method for estimat- 
ing uric acid, 319 
Lymphocytes, 58 



MACKOCYTELEMIA, 48 
Magnesia mixture, 277 

soaps of, in the urine, 428 
Magnesium phosphate, 421 
Malaria, plasmodium of, 77 
Maltose, 383 

Mammary secretion, 484 
Marrow cells, 59 
Mason's lung (see Siderosis). 
Mastzellen, 59 
Meconium, 209 
Megaloblasts, 50 
Megalocytes, 48 
Melanaemia, 83, 398 
Melanin in the urine, 398 

tests for, 399, 447 
Melanogen, 398 
Melithsemia 'see Glycosuria). 
Membranous dysmenorrhea, vaginal dis- 
charge in. 481 
Meningeal fluid, examination of, 474 
Menstruation, vaginal discharge in, 480 
Metalbumin in ovarian cysts, 471 

tests for, 471 
Methsemoglobin, 37 

sulphide, 35 
Methsemoglobinaemia, 33 
Methane isee Marsh gas), 146 
Methyl-aniline violet test for hydro- 
chloric acid, 114 
staining bacteria, 228 
Methylene-blue, 92 
Methyl-violet, 228 
Microbes in pneumonic sputum, 236 
Micrococci in pus, 469 
Micrococcus gonorrhoeicus, 457 

urese, 455 
Microcythsemia, 48 
Microorganisms in the feces, 197 
in the milk. 487 
in the mouth, 89 
in the nasal secretion, 210 
in the pus, 469 
in the urine, 455 

in the vaginal discharges, 480, 481, 
482 
Microscopic examination of the blood, 48 
of the buccal secretion, 88 
of cystic fluids, 471 
of exudates, 464, 467 
of the feces, 162, 180 
of the gastric contents, 152 
of the nasal secretion, 210 
of the sputum, 220 
of transudates, 464 
of the urine, 416 
of the vaginal secretion, 479 
of the vomit, 152 
Miliary tuberculosis of the lung, urine 

in, 401 
Milk, 484 



INDEX. 



499 



Milk, chemical composition of, 486 

cows' -1ST 

in disease, 486 

examination of, 187 

fat in, estimation of, 489 

human, 486 

secretion of, in the adult female, 

485 
secretion of, in the newly born, 
484 

specific gravity of, 487 

witches', 484 

-curdling ferment in the gastric juice, 
126 

-sugar, 3S3 
Millon's reagent, 169, 364 
Mohr's test for hydrochloric acid, 114 
Monads, 183 

Motor-power of the stomach, examina- 
tion of, 155 

Leube's method, 155 

Salol test of Ewald and Sievers, 155 
Mucin, in the feces, 201 

in the urine, 352 

test for, 365 
Mucous corpuscles in the urine, 240 

cylinders in the feces, 177, 206 
Mucus, in the gastric contents, 149 

in the feces, 177 

in the urine, 352 
Murexid test, 317, 418 
Myeline granules in the sputum, 223 
Myelocytes, 59 



NASAL catarrh, 209 
secretion, 210 

cerebro-spinal fluid in, 209 
characteristics of, 209 
Charcot-Leyden crystals in, 209 
concretions in, 209 
in disease, 209 
Neisser, gonococcus of, 457 
Nematodes, 192 
Nephritis, acute, 460 
amyloid, 460 
chronic interstitial, 460 
parenchymatous, 460 
Nessler's reagent, 139 
Neutral phosphate of calcium in the 

urine, 4'21 
Neutrophilic granules in the blood, 58 
Nitric acid test for albumin, 354 
Nitrogen in the urine, 290 
estimation of, 308 
Nitrogenous equilibrium, 291 
Nitro-prusside of sodium, as a test for 

acetone (see Legal's test, 408). 
Normal acid solution, 101 

solution of sodium hvdrate, 104 
urobilin, 174, 384 
Normoblasts, 50 



Nose, secretion from, 209 
Nubecula in the urine, 240 
Nucleo-albumin, in the blood, 1 1 
in the urine 362 
test for, 365 
Ny lander's test for sugar, 277 



(1 



?DEMA of the lungs, sputum in, 237 
J Oidium albicans, 90, 165, 210, 231 

Oligochromasia, 29 

Oligocythemia, 29, 50 

Oliguria, 246 

Organic acids in the blood, 44, 45 

in the gastric juice, 144 

in the sputum, 233 

quantitative estimation of, II I 
Organized sediments of the urine, 432 
Ovarian cysts, 471 

Oxalate of calcium crystals in the spu- 
tum. •j; , .2 
in the urine, 418 
Oxalic acid in the urine, 331 

diathesis, 333 

properties of, 333 

quantitative estimation of, 334 
tests for, 334 
Oxaluria idiopathic^. 333 
Oxy-acids in the urine, 389 
Oxybutyric acid-/3 in the urine, 409 
Oxyhemoglobin, 18, 27 
Oxyuris vermicularis, 182, 193 
Ozaena, 210 



PACINI'S fluid, 66 
Pancreatic cysts, 473 

trypsin in, 473 
juice in the gastric contents, 150 
Paracresol in the urine, 405 
Paramoecium coli, 186 
Parasites in the blood, 72 
in the feces, 182 
in the gastric contents, 152 
in the urine, 455 
malarial, 77 
Pathologic albuminuria, 336 
acetonuria, 407 
glycosuria. 369 
urobilin, 384 
Pepsin in the gastric juice, 123 

quantitative estimation of 
125 
tests for, 125 
Pepsinogen in the gastric juice, 123 
estimation of, 126 
tests for. 125 
Peptones in the blood, 41 
in the feces, 201 
in the gastric juice, 133 

tests for, 133 
in the urine, 348 



500 



INDEX. 



Peptones in the urine, tests for, 364 
Peptonuria, 349 

enterogenic, 349 

hematogenic, 349 

hepatogenic, 349 

histogenic, 349 

pyogenic, 349 

renal, 349 

vesical, 349 
Pernicious anaemia, blood in, 85 
Persistent glycosuria, 369 
Pettenkoffer's test, 47 
Phagocytes, 52 
Phagocytosis, 52 

Pharyngomvcosis leptothricia, 91 
Phenol, 281 

estimation of, 406 

in the feces, 168 

in the urine, 399, 405 
test for, 406 
Phenyl-glucosazon, 375 

-hydrazin chloride, 375 
Phloroglucin-vanillin test for hydro- 
chloric acid, 113 
Phosphates in the urine, 270 

estimation of, 277 

separate estimation of alkaline and 
earthy, 280 
tests for, 276 
Phosphatic sediment in the urine, 414 
Phosphoric acid, estimation of, in the 

urine, 277 
Phthisis pulmonalis. sputum in, 236 
Physiologic acetonuria, 407 

albuminuria, 336 

glycosuria, 368 
Picric-acid test for albumin, 360 
Pigments in the feces, 173 

in the urine, 384, 400 
Piria's test for tyrosin, 426 
Plaques, 64 
Plasma of the blood, 1 
Plasmodium malariae, 77 
Plastic bronchitis (see Fibrinous), 235 
Platodes, 182 
Pneumaturia, 200 
Pneumoconioses, 238 
Pneumonia, diplococcus of, 229 

sputum in, 236 
Poikilocytes, 49 
Poikilocytosis, 49 

Polarimeter isee Saccharimeter), 381 
Polycythemia, 50 
Polyuria 244 

epicritic form of, 245 
Preparation of cover-glasses, 60, 228 
Prostatic fluid, 476 
Proteids formed in the stomach, 128 

of the blood, 40 
Proteoses, 129 
Protozoa, 183 

in the feces, 1 83 



Protozoa in the pus, 469 

in the sputum, 225 

in the urine, 459 

malarial, 77 
Pseudo-casts, 443 

leukaemia, blood changes in, 85 
Ptomaines, in the gastric contents, 
148 

in the urine, 412 
Ptyalin, 87 
Pulmonary diseases, sputum in, 234 

abscess, 235 

gangrene, 234 

oedema, 237 
Purulent exudates (see Pus), 466 
Pus, 466 

chemistry of 467 

crystals in, 470 

detritus in, 468 

general characteristics of, 466 

giant-corpuscles in, 468 

in the feces, 177, 181 

in the gastric contents, 151 

in the urine, 435 
tests for, 437 

leucocytes in, 467 

microscopic examination of, 467 

parasites in, 469 

red corpuscles in, 468 
Putrescin, 412 
Putrid bronchitis, 234 

exudates, 466 
Pycnometer, 251 
Pyelonephritis, 438 
Pyogenic peptonuria, 349 
Pyrocatechin in the urine, 407 
Pyuria, 435 



QUARTAN ague, plasmodium malariae 
in, 80 
Quevenne's lactodensimeter, 409 



REACTION, of the blood, 20 
of the feces, 166 

of the gastric juice, 102 

of the urine. 253 
Red blood -corpuscles, 48 
Relapsing fever, spirillum of, 75 
Renal albuminuria, 339 

epithelium, 434 
Resorcin test, 114 

Resorptive power of the stomach, exami- 
nation of, 156 
Reynold's test for acetone, 408 
Rhabdonemastrongvloides, 183 
Rhinoliths, 210 
Rhubarb in the urine, 384 
Rice-water stools, 178 
Rosenbach's reaction, 391 

test for bile-pigments, 396 



INDEX. 



501 



Round worms, 1 92 
Rust-colored expectoration, 236 



SACCHARI METER of Einhorn, 375, 
380 
of Soleil-Venteke, 381 

Saccharomyces cerevisioe (see Yeast). 
Sago-grain forms in the feces, 178 
Salicylic acid, test for, in the urine, 399 
Saliva, 8(5 

chemistry of, $<o 
in the gastric contents, 150 
in special diseases of the mouth, 90 
microscopic examination of, 88 
pathologic alterations of, 89 
test for sulpho-cyanides, 87 
Salivary corpuscles, 88 
Salol, test for, in the urine, 399 

of Ewald and Sievers, 155 
Santonin in the urine, 384 
Sarcina pulmonalis, 231 
urinoe, 456 
ventriculi, 153 
Scherer's test for leucin, 427 
Schizomycetes in the feces, 165 
Scybahe, 175 
Sediments in the urine, 412 

ammonio-magnesium-phos- 

phate in, 420, 431 
ammonium urate in, 430 
amorphous urates in, 418 
basic magnesium phosphate in, 

421 
basic phosphate of calcium and 

magnesium. 430 
bilirubin in, 428 
calcium carbonate in, 431 
oxalate in, 418 
sulphate in, 423 
cystin in, 423 
epithelial cells in, 432 
fat in, 429 

foreign bodies in, 459 
hsematoidin in, 428 
hippuric acid in, 422 
in acid urines, 416 
in alkaline urines, 430 
indigo in, 431 
leucin in, 424 
leucocytes in, 435 
mode of examination of, 415 
monocalcium phosphate in, 421 
neutral calcium phosphate in, 

421 
non organized, 416 
organized, 432 
parasites in, 455 
red corpuscles in, 440 
soaps of lime and magnesia in 

428 
spermatozoa in, 453 



Sediments in the urine, tube-casts in, 4-13 
tumor- particles in, 459 
ty rosin in, 424 
uric aeid in, 41(1 
xanthin in. 127 
Semen, 475 

chemistry of, 475 
general characteristics of, 475 
microscopic examination of, 476 
pathology of, 477 
recognition of, in stains, 477 
spermatic crystals in 475, 476 
spermatozoa in 476 
j Senna in the urine, 384 
Sepsis, organisms in the blood, 75 
Sero-purulent exudates, 464 
Serous exudates, 464 
Serum-albumin in the blood, 23 
in the urine, 335 
estimation of, 360 
tests for, 353 
-globulin in the blood, 23 
in the urine, 348 
estimation of, 363 
test for, 353 
Siderosis, 23 S 
Skatol in the feces, 168 
Skatoxyl.281 

sulphate, 405 
Smegma bacillus, 457 
Soaps of lime and magnesia, 428 
Soda solution, normal, 104 
Sodium chloride in hydatid fluid, 472 
Spectroscope, 38 
Spermatic crystals, 475, 476 
Spermatocystitis, 454 
Spermatorrhoea, 455 
Spermatozoa in the urine, 453 

in the semen, 476 
Spermin, 475, 476 
Spiegler's reagent, 360 
Spirals of Curschmann, 218 
Spirillum of relapsing fever, 75 
Spirochaeta Obermeieri, 75 
Sporozoa, 186 
Sputum, 211 

amount of, 212 

bacteria in, 225 

blood in, 214, 221 

cheesy particles in, 216 

chemistry of, 233 

color of, 213 

concretions in, 220 

configuration of 215 

consistence of, 213 

Curschmann's spirals in, 218 

crudum, 215 

crystals in, 231 

ecchinococcus membranes in, 220 

elastic tissue in, 216, 223 

fibrinous casts in, 217 

general characteristics of, 211 



502 



INDEX. 



Sputum, globosum, 215 

heterogeneous, 215 

homogeneous, 215 

in various diseases, 234 

microscopic examination of, 220 

nummular, 215 

odor of, 214 

parasites in, 224, 225 

specific graviiy of, 215 

technique in the examination of, 211 
Staining of blood, 60 

of tubercle bacilli. 228 
Starch, digestion of, 130 
Stercobilin, 173, 397 
Stoke's fluid, 27 
Stomach, atrophy of, 159 

cancer of, 159 

contractile power of, 155 

dilatation of, 159 

mucous gastritis of, 159 

rate of absorption in, 156 

-tube, 97 

contraindications to its use, 97 
its introduction, 98 

"washing, 99 
Stomatitis, catarrhal, 90 

ulcerative, 90 
Stools (see Feces). 
Strongyloides, 194 
Strongylus duodenalis, 194 
Stycosis, 238 

Succinic acid in hydatid fluid, 472 
Sugar in the blood, 25, 41 

in the urine, 367 (see Glucose) 
Sulphanilic acid test (see Ehrlich s re- 
action). 
Sulphates in the urine, 280 
estimation of, 285 
tests for, 284 
Sulpho-cyanide of potassium solution, 

266 
Sulpho-cyanides in the saliva, 87 
Sulphuretted hydrogen in the urine, 411 

tests for, 411 
Syntonin, 129 

test for, 132 



TJ£NTA cucumerina, 190 
echinococcus, 225 

flavo punctata, 190 

medio canellata (see T. saginata). 

nana, 182, 189 

saginata, 182, 187 

solium, 182, 188 
Tartar, 91 

Tartrate of potassium and sodium, 373 
Teichmann's crystals, 36 
Test-breakfast of Boas, 97 

of Ewald and Boas, 96 

-dinner of Riegel, 96 

-meal of Salzer, 96 



Test-meals, 95 

Thoma-Zeiss' hsemocvtometer, 65 

Thrush, 90 

Titration method for estimating sugar, 

377 
Toison's fluid, 66 
Tongue, coating of, 91 
Tonsils, coating of, 91 
Topfer's test for hydrochloric acid, 112 
Toxalbumins in the gastric contents, 148 
Transitory glycosuria, 368 
Transudates, 461 

albumin in, 462 
chemistry of, 463 
coagulation of, 463 
general characteristics of, 461 
microscopic examination of, 464 
specific gravity of, 461 
Trematodes, 190 
Tribromophenol, 496 
Trichina spiralis, 195 
Trichocephalus dispar, 182, 194 
Trichomonas intestinalis, 186 

vaginalis, 479 
Trichotrachelides, 183 
Triple-phosphate crystals in the sputum, 
233 
in the urine, 420 
Tripperfaden, 439 
Tromner's test, 372 

Tropseolin test for hydrochloric acid, 114 
Trypsin, in pancreatic cysts, 473 

test for, 473 
Tube-casts in the urine, 443 
amyloid, 447. 448 
clinical significance of, 451 
compound hyaline, 444 
fatty, 447 
formation of, 450 
granular, 444 
hyaline, 444 

mode of examination, 443 
pseudo, 448 
pus, 452 
true, 444 
waxy, 447 
Tubercle bacilli, detection of, 225 
in the blood, 73 
in the feces, 200 
in the milk, 487 
in the pus, 469 
in the sputum, 225 
in the urine, 456 
Tumor-particles in the gastric contents, 
154 
in the urine, 459 
Typhoid fever, bacillus of, 198 
in the blood, 74 
in the feces, 209 
Ehrlich's reaction in, 401 
Tyrosin in the feces, 168 
in the sputum, 215, 232 



INDEX. 



503 



Tyrosin in the urine. 293, 1-1 
tests for, 424 



UFFELM ANN'S test for lactic acid, 
137 
Ulcer of the stomach, 159 
Unorganized sediments in urines, 416 
Uraemia, 43 

Uranium solution, 277 
Urates in urinary sediments, 418 
Urea in the blood, 43 
in the urine, 287 

estimation of, 300 
separation of, 298 
tests for, 298 
nitrate, 297 
oxalate. 297 
Ureometers, 300 
Doremus', 306 
Green's, 306 
Hiifner's, 306 
Simon's, 300 
Squibb's, 307 
Urethra, epithelium of, 435 
Urethritis, gonococcus in, 458 
Uric acid, crystals of, 41 6 
diathesis, 313 
estimation of, 317 

Haycraft's method, 317 
Heintze's method, 321 
Ludwig-Salkowski's me- 
thod, 319 
in the blood, 44 
in the urine, 311 
properties of, 315 
test for, 317 
Urinary cylinders (see Tube-casts), 443 

sediments, 412 
Urine, 239 

acetone in 407 
acidity of, 257 
albumins in, 235 
alkaptonin, 399 
benzoic acid in, 325 
bile acids in, 396 
bile-pigments in, 393 
blood in, 366, 440 
carbohydrates in, 366 
casts in, 443 
chemistry of, 258 
chlorides in, 260 
chromogens in, 384 
chyle in, 410 
color of, 241 
consistence of, 243 
diacetic acid in, 408 
Ehrlich's reaction in, 401 
epithelium in, 432 
fat in, 410 < 
fatty acids in, 410 
fecal matter in, 459 



Urine, ferments in, 411 

foreign bodies in, 459 

gases in, 411 

general appearance of, 240 

general chemical composition of, 258 

kreatin in, 326 

kreatinin in, 326 

lactic acid in, 410 

leucocytes in, 435 

microscopic examination of, 416 

mineral ash, estimation of, 259 

nitrogen in, 290, 308 

nubecula in, 240 

odor of 242 

organized sediment of, 432 

oxalic acid in, 331 

oxaluric acid in, 332 

oxybutyric acid in, 409 

parasites in, 458 

phenol in 399, 405 

phosphates in, 270 

pigments in, 384 

ptomaines in, 412 

pus in, 436 

pyrocatechin in, 399 

quantity of, 243 

reaction of, 253 

sediments in, 412 

solids in, 252 

specific gravity of, 247 

spermatozoa in, 453 

sugar in, 367 

sulphates in, 280 

urea in, 287 

uric acid in, 311 

xanthin bases in, 331 
Urines, blue, 389, 400 

green, 400 
Urinometer, 250 
Urobilin, febrile, 398 

normal, 174, 384 

pathologic, 384, 396 
Urobilinogen, 397 
Urobilinuria. 397 
Urochrome, 384 
Uroerythrin, 385 
Urofuscohsematin, 392 
Urohaematin, 390 
Urohsematoporphyrin, 393 
Urorosein, 391 
Uroroseinogen, 391 
Urorubrohaematin, 392 



AGINAL blennorrhcea, 480 
discharge, 479 

during menstruation, 480 
general description of, 479 
in abortion, 482 
in gonorrhoea, 482 
in membranous dysmenorrhea, 
481 



504 



INDEX. 



Vaginal discharge in uterine 
482 
in vaginitis, 481 
in vulvitis, 481 
Valeur globulaire, 31 
Vanillin, 113 
Vermes, in the blood, 83 

in the feces, 187 

in the sputum, 225 

in the urine, 459 
Vesical epithelium, 435 
Vi tali's test for pus, 437 
Vomited material, 148 
Vomitus matutinus, 106, 150 
Von Fleischl's haemometer, 29 



cancer, Whetstone crystals (see Uric acid). 

White blood-corpuscles (see Leuco- 
cytes). 
Whooping-cough, sputum in, 230 
Worms i see Vermes). 



XANTHIN bases in the blood, 44, 45 
in the urine, 331 
Xantho-proteic reaction, 170 



VEAST-CELLS in the gastric contents, 
1 153 

in the urine, 456 



WAXY casts, 447 
Weigert-Ehrlich's stain, 228 
Weyl's test for kreatinin. 328 



ZIEHL-XEELSEX stain, 228 
Zymogens in the gastric juice, 123 



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